The Effect of Pomegranate Juice on the Expression of Some Murine UDP-Glucuronosyltransferases Genes.

BACKGROUND: Food-drug interactions may lead to suppression or induction of drug metabolizing enzymes. Pomegranate is a commonly used fruit in folk medicine all over the world. Data concerning the effect of pomegranate on the activity of UDP-glucuronosyltransferases (UGTs) is scarce. OBJECTIVE: The purpose of this work was to investigate the effect of pomegranate juice ingestion on the transcription of ugt2b1, ugt2a3, and ugt1a9 in the liver and small intestine of male mice. METHODS: Pomegranate juice was administered to 10 male mice for 14 days in drinking bottles instead of water. Ten control mice received water in the drinking bottles. On the 15th day, the mice were sacrificed and the liver and the small intestine were removed. The small intestine was divided into 3 parts. Total mRNA was extracted from samples of these specimens, and cDNA was synthesized by quantitative real-time polymerase chain reaction (RT-PCR) using specific primers for each ugt gene. RESULTS: The ugt1a9 mRNA level was reduced by 2.25-fold in the liver and by 6-, 1.5-, and 3-folds in the first, second and third part of the small intestine, respectively. The ugt2b1 mRNA level in the liver and the third part of the small intestine was not affected, while it was reduced by 3.7- and 3-folds in the first and second parts of the small intestine, respectively. The ugt2a3 mRNA level was not affected in the liver and the 3 parts of the small intestine. CONCLUSION: Some ugt mRNA levels may be reduced by the ingestion of pomegranate juice, which may reduce the metabolism of their drug substrates. The consequences may be an accumulation of such drugs in the body and enhanced toxicity.

SLCO1B1 Gene Polymorphisms (rs2306283 and rs4149056) and Statin-Induced Myopathy in Jordanian Diabetics.

BACKGROUND: The use of statins to lower high serum cholesterol levels may be associated with a number of adverse reactions, including severe myopathy. The solute carrier organic anion transporter 1B1 (SLCO1B1) gene, which encodes the organic anion-transporting polypeptide OATP1B1, is related to the intracellular transport of statins. The aim of this research was to study the association of rs2306283 and rs4149056 genetic polymorphism of the SLCO1B1 gene with the development of statin-induced myopathy in Jordanian diabetics receiving statins. METHODS: We included 413 patients attending the Diabetes Clinics of the National Center for Diabetes, Endocrinology and Genetics, Amman, Jordan. The study was approved by the Institutional Review Board of NCDEG. Myopathy was defined as the elevation of creatine kinase more than 3 times the upper limit of normal. Every subject signed an informed consent form and donated 3-5 mL of venous blood. Genome DNA was extracted from lymphocytes of peripheral blood. Genotypes were identified using the Tetra Amplification Refractory Mutation System of SLCO1B1. RESULTS: The minor allele frequencies of rs2306283 [G] and rs4149056 [C] were 0.38 and 0.23, respectively. The two SNPs followed the Hardy-Weinberg equilibrium. The development of SIM was significantly associated with the homozygous and heterozygous minor allele genotype of rs4149056 (CC and CT), and the homozygous wild type allele genotype of rs2306283 (AA). There was no linkage disequilibrium between the two SNPs in the studied subgroups. CONCLUSION: Genetic polymorphism in the SLCO1B1 Gene is a risk factor for the development of SIM in Jordanian patients.

Association of rs7041 and rs4588 Polymorphisms of the Vitamin D Binding Protein and the rs10741657 Polymorphism of CYP2R1 with Vitamin D Status Among Jordanian Patients.

AIM: Previous studies have shown a high prevalence of vitamin D deficiency among Jordanians despite adequate exposure to sunlight, suggesting the presence of other causes for this deficiency. The aim of this study was to identify the relationship between 25-hydroxyvitamin D [25-(OH) VD] status and the nonsynonymous single-nucleotide polymorphisms (SNPs) (rs7041 and rs4588) of the GC gene, which encodes the vitamin D binding protein, and one SNP (rs10741657) near the CYP2R1 gene. METHODS: Blood samples from 381 subjects (74 males and 307 females, 18-60 years of age) were obtained from the "National Center for Diabetes, Endocrinology and Genetics" (Amman, Jordan). The subjects were classified as "apparently healthy" if they did not suffer from chronic diseases and as "unhealthy" if they suffered from certain chronic diseases. Subjects' genotypes for GC; rs7041 and rs4588; CYP2R1; rs10741657 were determined by the polymerase chain reaction-restriction fragment length polymorphism assay method. RESULTS: Apparently, healthy subjects had significantly higher 25-(OH) VD levels than unhealthy patients. In apparently healthy subjects, the rs10743657 genotypes containing the variant allele A (AA, GA) were associated with higher 25-(OH) VD levels than the homozygous wild-type genotype (GG). The genotypes containing the variant allele of rs7041 (TT, TG) and rs4588 (AA, AC) were associated with lower 25-(OH) VD levels than the wild-type genotypes (GG and CC, respectively). Haplotype analysis of rs7041 and rs4588 revealed that the haplotypes GC1S and GC1S/S were associated with 25-(OH) VD sufficiency, whereas haplotypes GC1F/S, GC1F/2, GC1S/2, GC2, and GC2/2 were associated with 25-(OH) VD deficiency. In unhealthy patients, only the homozygous genotype of the variant allele of rs7041 (TT) was associated with higher 25-(OH) VD levels, which is the reverse of what had been observed in apparently healthy subjects. CONCLUSIONS: The rs70141657G/A of CYP2R1 and rs7041T/G and rs4588C/A of vitamin D binding protein genetic polymorphisms were associated with increased risk of vitamin D deficiency among apparently healthy Jordanians.

Methylene tetrahydrofolate reductase genotypes frequencies: association with toxicity and response to methotrexate in rheumatoid arthritis patients.

OBJECTIVES: The purpose of this study was to determine the genotype/allele frequencies of C677T and A1298C polymorphisms of methylenetetrahydrofolate (MTHFR) gene in Jordanian rheumatoid arthritis (RA) patients. In addition, the association between MTHFR gene C677T and A1298C polymorphisms and response to and toxicity of methotrexate (MTX) was evaluated. METHODS: 159 adult rheumatoid arthritis ent Rheumatology Clinic at The Jordan University Hospital, between December, 2011 and April, 2012 were recruited into the study. Genomic DNA was extracted from leukocytes using Wizard Genomic DNA extraction Kit. The DNA extracts were amplified by polymerase chain reaction (PCR), and the PCR products were subjected to restriction enzymes to identify the C677T and A1298C genotypes. Genotype frequencies were identified and their relationship to some measures of MTX response and toxicity were evaluated. RESULTS: The 677 TT genotype frequency was higher in RA patients (15.1%) compared to the healthy control group (5.9%) (odds ratio 3.09, 95% confidence interval (CI) 1.39-6.87, p-value=0.0056). No such differences were seen with the A1298C genotypes. The frequencies of 677T and 1298C variant alleles were 0.346 and 0.296, respectively. None of the change-in-disease-activity measurements in MTX-treated patients has a significant association with the various genotypes. There was no significant association between A1298C genotypes and "œany MTX toxicity", but there was an association between C677T polymorphism and "œany MTX toxicity" (p=0.037). In addition, there was no association between both SNPs and specific MTX adverse effects. However, some haplotypes or combinations of the C677T and A1298C genotypes were associated with certain MTX side effects. CONCLUSIONS: More data from a larger number of RA patients are needed to evaluate the role of pharmacogenetic studies of MTHFR gene in predicting MTX response and toxicity.

Association of MDR1 C3435T and RFC1 G80A polymorphisms with methotrexate toxicity and response in Jordanian rheumatoid arthritis patients.

OBJECTIVES: Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA). Genetic polymorphisms of reduced folate carrier (RFC1 G80A) and multi-drug resistance-1 (MDR1 C3435T) might affect MTX response and/or toxicity. The aim of this study was to find out if there is an association between those polymorphisms and MTX toxicity and/or response in Jordanian RA patients. METHOD: A genotyping approach was used to determine the studied polymorphisms in 159 RA patients. RESULTS: There was an association between RFC1 G80A and MDR1 C3435T polymorphisms with MTX toxicity. Patients with RFC1 80GG genotype were at higher risk for gastrointestinal toxicity (p = 0.036). Patients carrying at least one MDR1 3435T variant allele were at higher risk for MTX overall toxicity (p = 0.04), especially hepatotoxicity (p = 0.028). Furthermore, the distribution of RFC1 G80A polymorphism between males and females was significantly different. The variant genotype 80AA was found to be more in males than in females (60% vs. 31%) (p = 0.011). CONCLUSIONS: Our results suggest that genetic polymorphisms in methotrexate transporters affect the toxicity but not the response of MTX treatment. Further studies should be performed to have more conclusive results.

The effect of pomelo mix ethyl acetate extract on CYP3A6 and P-glycoprotein gene transcripts in rabbits.

Pomelo fruit juice and pomelo ethylacetate extract have been shown to increase the bioavailability of some CYP3A substrates. The purpose of this study was to investigate if this effect might be contributed to by changes in CYP3A and p-glycoprotein mRNAs levels in the liver and proximal small intestine. The ethyl acetate extract of pomelo mix was administered for 7 days to 10 rabbits. Nine rabbits were administered tap water for 7 days. The administration was through oral intubation to the stomach. On the 8(th) day, the rabbits were sacrificed, and the liver and the proximal 15 cm of the small intestine were dissected. Total RNA was extracted from the specimens and cDNA was prepared by quantitative real-time-polymerase chain reaction (RT-PCR) using specific primers. The ethyl acetate extract of pomelo mix reduced the mRNA expression of CYP3A6 almost 5-folds in the intestine and 2-folds in the liver. In contrast, a 1-fold increase to the p-glycoprotein mRNA expression was observed under the same experimental conditions. In conclusion, the ethyl acetate extract of pomelo mix reduced the mRNA expression of CYP3A6 in both intestine and liver but to different degrees, while the p-glycoprotein mRNA expression was not reduced.

The A(1166)C polymorphism of the AT1R gene is associated with an early onset of hypertension and high waist circumference in Jordanian males attending the Jordan University Hospital.

There is no agreement on the involvement of angiotensin II type 1 receptor (AT1R) gene A(1166)C variant and essential hypertension. The purpose of this study was to investigate the association between angiotensin II type 1 receptor (AT1R) gene A(1166)C variants with essential hypertension and some related parameters in a sample of Jordanian hypertensive patients. DNA samples from 108 hypertensive individuals and 102 age- and gender-matched non-hypertensive controls of the Jordanian population were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism assay (PCR-RFLP) methods to determine the frequency of A(1166)C variants alleles. No statistically significant differences were found in the distribution of alleles and genotypes between hypertensive and non-hypertensive individuals, not even after gender segregation. The frequency of the variant allele (C(1166)) was significantly higher in the early-onset compared to the late-onset group of hypertensive males, in subjects with positive family history of hypertension, and in subjects with high waist circumference. In conclusion, the A(1166)C polymorphism is not associated with essential hypertension in Jordanian hypertensive individuals. However, it was associated with an early onset of hypertension in males, with positive family history of hypertension, and with high waist circumference irrespective of blood pressure status.

N-acetyltransferase-2 genotypes among Jordanian patients with diabetes mellitus.

BACKGROUND: There are inconsistent reports concerning N-acetyltransferase 2 (NAT2) genotypes in diabetes mellitus (DM). OBJECTIVE: The objective of the study was to explore any association between NAT2 genotypes and Type 1 and Type 2 DM in Jordanians. METHODS: 106 Type 1 and 110 Type 2 DM patients attending the "National Center for Diabetes, Endocrinology and Genetics", Amman, Jordan, were included in the study. DNA was extracted from venous blood using a commercial DNA extraction kit. NAT2 genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequency of the genotype that encodes rapid acetylation (the wild-type genotype NAT2*4/4) was similar in the two types of diabetes mellitus. Those which encode intermediate acetylation (NAT2*4/5, NAT2*4/6, and NAT2*4/7) were higher in Type 2 diabetes (0.482) compared to Type 1 diabetes (0.339), while the frequency of genotypes which encode slow acetylation (NAT2*5/5, NAT2*5/6, NAT2*5/7, NAT2*6/6, NAT2*6/7, and NAT2*7/7) were higher in Type 1 diabetes (0.547) compared to Type 2 diabetes (0.418). CONCLUSION: There is excess of genotypes encoding intermediate acetylation in Type 2 DM and an excess of slow acetylator genotypes in Type 1 DM. Furthermore, NAT2*4/6 genotype (which encodes intermediate acetylation) was more prevalent in Type 2 DM. Type 1 DM behaved similar to non-diabetic controls in regard to acetylation status.

Thiopurine S-methytransferase gene polymorphism in rheumatoid arthritis.

BACKGROUND AND AIMS: Thiopurine S-methyltransferase (TPMT) is responsible for inactivation of thiopurine drugs which are commonly used in leukemia, organ transplantation and autoimmune diseases. The gene encoding TPMT is polymorphic, and both phenotyping and genotyping studies have shown ethnic variations in gene sequence and enzyme activity worldwide. The aim of this study is to identify the most common genetic polymorphisms of TPMT in healthy Jordanian volunteers and patients with rheumatoid arthritis (RA). METHODS: A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used to identify the frequency of TPMT (*2, *3A, *3B, and *3C) polymorphisms in 250 healthy Jordanian volunteers and 110 RA patients. RESULTS: Only four healthy subjects (1.6%) and one RA patient (0.9%) with variant alleles were identified in this study. Two healthy subjects had the TPMT*3A allele and the other two had the TPMT*3B allele, whereas the one RA patient had the TPMT*3A allele. No homozygous polymorphisms were detected and all genotypes detected were heterozygous (*1/*3A) (*1/*3B). None of the subjects had TPMT*2 or TPMT*3C variant alleles. CONCLUSIONS: Mutant alleles identified in this study have a low frequency. TPMT (*3A and *3B) were the only detected heterozygous alleles. No homozygous variant allele was detected. Further studies are necessary to identify other variant alleles that might uniquely occur in Jordanians.

Discrepancies between elderly patient's self-reported and prescribed medications: a social investigation.

AIMS: To study some characteristics of the elderly people attending the family practice clinic at the Jordan University Hospital (JUH) and to evaluate their knowledge of the prescribed drugs. METHODS: A total of 400 elderly people (180 men and 220 women) aged 71 ± 5.8 years were studied regarding sociodemographic characteristics and the use of medicinal and nonmedicinal remedies. In addition, agreement between self-reported drug information and information taken from the medical records was also evaluated. FINDINGS: Almost one-third of the patients had full agreement between their knowledge of total number of drugs they take and the numbers found in the medical records, whereas 43.4% underestimated and 21.8% overestimated these numbers. Five drugs/classes were accurately estimated by the patient (methyldopa, ezetimibe, warfarin, statins and antigout drugs). Underestimation was noticed in 17 drugs/classes and overestimation in 14. The significantly underestimated drug classes were biphoshponates, proton pump inhibitors, sulfonylureas and antiepileptic drugs. CONCLUSION: Some aspects of elderly people were evaluated regarding their medication knowledge. Almost two-third of the patients did not take their drugs in the proper way. The results of the study highlight the importance of taking several actions by all healthcare workers and by the community to optimise health care provided for elderly people.

Frequency of certain single-nucleotide polymorphisms and duplication of CYP2D6 in the Jordanian population.

The CYP2D6 isozymes are responsible for metabolism of 7-10% of clinically available drugs. Genetic polymorphism in CYP2D6 may have an impact on drug efficacy and toxicity. The aim of this study was to determine the allelic frequency of CYP2D6*4, *10, and *17 and CYP2D6*2×N duplication allele in 192 healthy unrelated male and female Jordanian volunteers. Polymerase chain reaction (PCR)-restriction fragment length polymorphism-based methods were used to identify the CYP2D6*4, *10, and *17 genotypes; and allele-specific long PCR was used to determine the CYP2D6*2×N allelic frequency. The CYP2D6*10 allele was the most frequent mutant allele in Jordanians (14.8%) followed by CYP2D6*4 and *17 at 12.8%, and 8.3%, respectively. The duplication allele was found in 13.5% of the studied sample. The CYP2D6*4 G-A heterozygote genotype frequency was 20.3%, and the homozygous mutant genotype was 2.6%. In case of CYP2D6*10 C-T and CYP2D6*17 G-C heterozygote genotypes, the frequencies were 21.4% and 12.5%, respectively, while the homozygous mutant genotype frequencies of T-T and C-C were 4.2% and 2.1%, respectively. In conclusion, the allelic distributions of the CYP2D6 gene among Jordanians are different from other Mediterranean groups, especially the *10 and *17 single-nucleotide polymorphisms, and more importantly the CYP2D6*2×N duplication allele, which seems to follow a gradient reduction in prevalence from Ethiopia to Northern Europe.

N-acetyltransferase-2 genotypes among patients with rheumatoid arthritis attending Jordan University Hospital.

AIM: To determine the frequency of major N-acetyltransferase (NAT2) alleles and genotypes among Jordanian patients with rheumatoid arthritis (RA). METHODS: The study was approved by the IRB of the Jordan University Hospital. An informed consent was signed by every patient. DNA samples from 150 healthy volunteers and 108 patients with RA were analyzed by polymerase chain reaction followed by a restriction fragment length polymorphism assay (PCR-RFLP) to determine the frequency of four major alleles: NAT2*4, NAT2*5, NAT2*6, and NAT2*7. RESULTS: The most prevalent genotypes are those that encode the slow acetylation phenotype. About 59.3% of the patients with RA carried the slow, 33.3% the intermediate, and 7.4% the fast-encoding genotypes. The frequency of NAT2 alleles was 0.241 (95% confidence interval [CI] 0.184-0.298) for NAT2*4, 0.449 (95% CI 0.383-0.515) for NAT2*5, 0.273 (95% CI 0.214-0.332) for NAT2*6, and 0.037 (95% CI 0.012-0.062) for NAT2*7 allele. The overall frequency of the slow acetylation genotype in patients with RA is similar to that in healthy Jordanian volunteers. However, the NAT2*5/7 genotype was found in seven patients (6.5%) with RA and was absent in Jordanian volunteers, and the z test revealed that the difference was statistically significant. This genotype constituted 10.9% of the genotypes encoding slow acetylation. CONCLUSION: The overall acetylator genotype in RA is similar to that in healthy volunteers. The overall slow acetylator genotypes do not seem to be a genetic risk factor for RA among Jordanians. However, the NAT2*5/7 genotype seems to be related to RA. The nature of this relationship needs further clarification.

The effect of ethyl acetate extract of pomelo mix on systemic exposure of verapamil in rabbits.

The effect of ethyl acetate extract of pomelo fruit on systemic exposure of verapamil was explored in rabbits. Two groups each of 8 locally-inbred New Zealand male rabbits were used. The first group was used for single-dose treatment (both verapamil and pomelo extract). The second group was used for multiple-dose treatment, pomelo extract (once daily for 14 days) and verapamil single doses (at days 7 and 14). A verapamil dose of 30 mg/kg and a pomelo extract dose of 45 mg/kg were used. Single-dose treatment with pomelo extract resulted in a minor change in mean C(max) of verapamil in plasma, while a decrease of 37.8% in AUC(0-24) and 28.3% in AUC(0-∞) was observed but did not reach statistical significance. After the first period of multiple dose treatment (pomelo extract for 7 days), the combination increased the concentration of verapamil in plasma with a significant increase in mean C(max), AUC(0-24) and AUC(0-∞) by 461.9%, 299.7%, and 261.1%, respectively (p values were 0.005, 0.002, and 0.006, respectively). In contrast, after the second period (day 14 of pomelo extract use), the combination decreased the concentration of verapamil in the plasma with a substantial decrease in mean C(max), AUC(0-24), and AUC(0-∞), by 68.2%, 69.7% and 58.3%, respectively. This decrease did not reach statistical significance (p values were 0.073, 0.081 and 0.083, respectively). The T(max) was not affected significantly in both studies. The study illustrates a complex time-dependent interaction between verapamil and the ethyl acetate extract of pomelo mix. More intensive studies are needed to further understand the nature of the interaction.

Effect of mint drink on metabolism of nicotine as measured by nicotine to cotinine ratio in urine of Jordanian smoking volunteers.

INTRODUCTION: Variation in nicotine metabolism may be due to genetic alterations in CYP 2A6, environmental factors, and diet. The purpose of this research was to evaluate mint drink effect on nicotine metabolism as judged by nicotine/cotinine ratio in urine of Jordanian smokers. METHODS: Twenty-four Jordanian smoker volunteers were allocated randomly into two groups. They either received mint drink 3 times a day for 1 week during the mint drink period or avoided menthol-containing products and mint drink for 1 week during the off-menthol period. One group treatment sequence was mint drink, off-menthol, while the other group treatment was off-menthol, mint drink. Early morning urine samples were collected at baseline and at the end of each period. Samples were analyzed by liquid chromatography-mass spectrometry for the nicotine and cotinine concentrations. Nicotine/cotinine ratio was calculated and compared among the different periods for each participant using the paired t test. RESULTS: All participants showed a consistent pattern of higher nicotine/cotinine ratios during mint drink compared with off-menthol periods, although to a variable extent. Mean nicotine/cotinine ratio during mint drink for all participants (1.327 ± 0.707) was higher than that during off-menthol (0.993 ± 0.547). Paired t test statistical analysis revealed a p < .0001. The mean difference in nicotine/cotinine ratio between the two periods was (-0.335), and the 95% confidence interval of the mean difference was (-0.451) - (-0.219). CONCLUSION: Mint drink increased nicotine/cotinine ratio in urine, suggesting a reduction in conversion of nicotine to cotinine.

The effect of licorice drink on the systemic exposure of verapamil in rabbits.

The effect of licorice root drink (aqueous extract of Glycyrrhiza glabra Fabaceae) on plasma concentration of verapamil, using rabbits as animal model, was investigated. Two groups of locally inbred New Zealand male rabbits were used. The first group was given a single dose of licorice drink (4 ml/kg body weight) concomitantly with 30 mg/kg verapamil, and the second group was given a daily dose of licorice drink (4 ml/kg body weight) for two weeks, with single doses of verapamil on days, 7 and 14. Single dose treatment resulted in a nonsignificant decrease in mean C(max) by 33.2% (P = 0.41), but in a significant decrease of AUC(0-24) and AUC(0-infinity) by 60.5% and 63.6%, respectively (P = 0.01). First period of multiple dose treatment study (7 days), resulted in a significant reduction in mean C(max), AUC(0-24) and AUC(0-infinity) by 55.0%, 47.0% and 45.7%, respectively (P = 0.02, 0.03 and 0.03, respectively). A more pronounced effect was seen at second period of multiple dose treatment study (14 days), where the corresponding decrease was, 85.4%, 76.8% and 73.3%, respectively (P < 0.01). Mean T(max) was significantly increased 4.2-fold over control period at day 14 of multiple dose study (P = 0.02). In conclusion, licorice root drink decreased verapamil systemic exposure both after single dose and after daily doses for 14 days.

Pharmacokinetics of gentamicin in hemodialysis patients: a comparative study between diabetic and non-diabetic patients.

Diabetic nephropathy is one of the leading causes of end-stage renal disease (ESRD). There is some evidence that differences in extracellular fluid volume and capillary permeability do exist between diabetic and non-diabetic patients. This may have an impact on the gentamicin volume of distribution and clearance and thus dosing regimen. The pharmacokinetic parameters of gentamicin [volume of distribution (Vd), clearance (CL), elimination rate constant (K), and half life of elimination (t((1/2)))] were studied before hemodialysis in 20 non-diabetic patients (controls) and 20 diabetic patients, in addition to its hemodialysis clearance.There were no statistically significant differences in Vd, CL, K, and t((1/2)) of gentamicin between the control and diabetic group. Therefore, a composite Vd of 0.25 l/kg and clearance of 0.063 ml/min/kg are suggested for dose calculation for both groups of patients. The mean hemodialysis clearance of gentamicin was higher in the diabetic (87.3 ml/min) than the control group (68.5 ml/min), comparing means by the unpaired t-test (P = 0.018).In conclusion, the same method can be used to calculate the loading dose of gentamicin in ESRD patients between dialysis sessions in both controls and diabetics, whereas, diabetics are expected to receive a higher replacement dose after the end of dialysis.

Pharmacoepidemiological study of prescription pattern of analgesics, antipyretics, and nonsteroidal anti-inflammatory drugs at a tertiary health care center.

OBJECTIVE: To examine the outpatients' prescribing pattern of doctors to analgesics, antipyretics, and nonsteroidal anti-inflammatory drugs (NSAIDs) at a tertiary care setting in Southwestern Saudi Arabia. METHODS: A retrospective review of one-year outpatient prescriptions kept by the pharmacy department at Aseer Central Hospital during the period 8 April, 2000 until 7 April, 2001. Five working days per week of each season were sampled randomly and systemically as every other prescription. The type and number of drugs prescribed, patient's diagnoses and age, and the prescribing physician were analyzed. The study sample included 3796 prescriptions. RESULTS: There was no significant seasonal variation in the pattern of prescription. The most commonly prescribed agent was paracetamol followed in decreasing frequency by ibuprofen, diclofenac, and aspirin. In few of the prescriptions combination of analgesics, antipyretics, and NSAIDs were used. One fourth of prescriptions, the diagnosis was not mentioned or was not clearly written, infection in 40%, and musculoskeletal disorders in 17.7%. The rest were a variety of problems for some of which, the drugs were used inappropriately. Aspirin was used exclusively in adults for cardio-protection, while paracetamol was used mainly as analgesic-antipyretic over all age groups CONCLUSION: Some of prescriptions suffered from significant deficiencies. In light of the serious adverse effects of analgesics, antipyretics and NSAIDs, education of physicians on rational use of such drugs, and prescription writing seems necessary.

Appropriateness of requests for therapeutic drug monitoring of antiepileptic drugs: the experience in southwestern Saudi Arabia.

The purpose of this study was to evaluate request forms of therapeutic drug monitoring of antiepileptic drugs for appropriateness criteria according to published data. Request forms received by the laboratory were sampled as all requests in one day per week on an alternating basis. Drugs monitored were phenytoin (PHT), phenobarbital (PB), carbamazepine (CBZ) and valproic acid (VPA). A total of 420 request forms were collected. Age, gender and weight were provided in 95.5%, 97.1% and 56.9% of request forms, respectively. The diagnosis, seizure type and the indication for therapeutic drug monitoring were provided in 81.6%, 3.2% and 55.5%, respectively. Sampling times were provided in 45% and were considered appropriate in 25.2% of the request forms. The indications for therapeutic drug-monitoring were considered appropriate in 28.6% of the request forms, and only 19.2% of these were appropriately sampled. Only 37.9% of all samples were drawn at steady-state. Serum albumin and creatinine concentrations were lacking in 93.6% and 53.3% of requests, respectively. The potential for drug-drug interactions was detected in 28.6% of all requests. Thus, the information needed for the proper interpretation of therapeutic drug monitoring results and that was provided in the request forms was surprisingly scarce. Most of the appropriateness criteria for therapeutic drug monitoring were not met.

A pharmacoepidemiological study of prescription pattern in outpatient clinics in Southwestern Saudi Arabia.

OBJECTIVE: To study the pattern of prescriptions in outpatient clinics in a teaching hospital in Southwestern Saudi Arabia. METHODS: A total of 3796 prescriptions from outpatient clinics of Aseer Central Hospital, Abha, Kingdom of Saudi Arabia were screened randomly and systemically over one-year period (April 2000 to April 2001). The prescriptions were analyzed for the essential elements of the prescription order, and for the number and classes of drugs prescribed, source of prescription and appropriateness of prescription to the diagnosis. RESULTS: The source of prescriptions was not provided in 61.5% of prescriptions. The diagnosis was missing in 15.1% and not readable in 18.9% of prescriptions. Upper respiratory tract infection (URTI) was the most frequent diagnosis and was included in 21.6% of prescriptions. The average number of drugs per prescription was 2.1 +/- 1.05 (Mean +/- SD), with 90.8% of prescriptions containing 3 or fewer drugs. The most frequently prescribed drugs were nonsteroidal anti-inflammatory drugs (NSAIDs), including paracetamol which were included in 51.2% of prescriptions, followed by antibacterial agents (33.2%). Only 46.4% of prescriptions were appropriate to the diagnosis, while 11.1% were partially appropriate and 5.3% were inappropriate. For the rest (37.2%), it was difficult to evaluate appropriateness due to deficient information. General practitioners and specialists were more likely to prescribe appropriately than emergency room physicians (64.6% and 60.4% versus 35.7%). None of the prescriptions for antiplatelet and anticoagulant drugs and antihypertensive agents were inappropriate. CONCLUSION: These results emphasize the need for continuing medical education on rational prescribing, and for periodic monitoring of physicians habits on drug utilization.