Disposition kinetics of omeprazole in healthy female volunteers in Pakistan

Omeprazole [OMP] a proton pump inhibitor is widely used to suppress gastric acid secretions of parietal cells of stomach and metabolized predominantly by CYP2C19. The objective of the present study was to investigate the pharmacokinetics and dosage regimen of OMP, after its single oral administration in eight healthy adult female subjects. Blood samples were collected at different time intervals after oral administration and their pH was measured. Plasma concentration of OMP was determined by high performance liquid chromatography [HPLC] system equipped with UVvisible Detector. The concentration versus time data was used to compute the pharmacokinetic parameters with the help of computer software programme MW/PHRAM APO version 3.02.Peak plasma concentration was [Cmax] 0.38 +/- 0.04 microg/ml achieved at 2.07 +/- 0.22 hrs. The elimination half-life [t1/2beta] was1.82 +/- 0.42 hrs. Volume of distribution [Vd] in the present study was 0.40 +/- 0.07 l/kg with total body clearance [ClB] 0.19 +/- 0.02 l/hr/kg and area under the curve [AUC] 1.89 +/- 0.23 microg.hr/ml. The pharmacokinetic properties which are different from the literature after oral administration of 20 mg OMP in eight healthy female volunteers may be due to the variations of environment and genetic variation between Pakistan and drug manufacturing of foreign countries

Renal clearance and urinary excretion of omeprazole in healthy female volunteers in Pakistan

Omeprazole is a widely prescribed proton pump inhibitor to treat various gastric acid hyper secretion disorders. The present study was designed to evaluate the renal clearance and urinary excretion of omeprazole in eight healthy female volunteers to increase the understanding of the contributing factors such as demographics variability in the renal clearance and urinary excretion of omeprazole under indigenous conditions. The urine and blood samples were collected 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours after oral administration of enteric coated omeprazole [20 mg] and drug concentration in the samples was determined by High Performance Liquid Chromatography [HPLC] with C18 column and UV detector. Urinary excretion and renal clearance of omeprazole was calculated and data was statistically analyzed by using regression/correlation technique. Endogenous creatinine was also measured by reagent kit available in the market. The results indicate that mean diuresis was 0.0172+/-0.0029 ml/min/kg. While the mean values of renal clearance of creatinine and omeprazole were 1.315+/-0.103 and 0.066+/-0.0042 ml/min. kg, respectively. Whereas, clearance ratio was 0.055+/-0.007 which indicates back diffusion. The cumulative percentage of dose excreted was 6.71+/-0.358. A significant [p<0.05] negative correlation [r= -0.457] between clearance ratio and urine pH of omeprazole reflecting glomerular filtration reabsorption of drug at kidney tubular level while significant [p<0.05] negative correlation [r= - 0.681] between clearance ratio and plasma concentration of omeprazole indicates the involvement of active tubular secretion of drug. It can be concluded that during glomerular filtration, omeprazole diffuse back/reabsorption. Therefore, Urinary excretion of omeprazole in indigenous healthy female subjects was observed to be lower than given in the literature values

Identification of ofloxacin-resistant mycobacterium tuberculosis by PCR-RFLP and sequencing

This study was planned to verify the resistance frequency of Ofloxacin [OFX] against Mycobacterium tuberculosis by polymerase chain reaction restriction fragment length polymorphism [PCR-RFLP] technique and sequencing. Total 366 clinical samples of suspected TB patients were collected from various localities of central Punjab. All of them were found positive by ZN [Zeihl-Nelsen] staining method. Among them, 108 [29.5%] were found negative and 258 [70.5%] positive on PCR based study. The cases not responding to ATT were further characterized by proportion method and by PCR-RFLP to establish the drug resistance. Selected drug resistant case were further sequenced to confirm the results of amplified RFLP. The results showed that out of 118 drug resistant cases, 06 [5.08%], 03 [2.54%] were found resistant to OFX by drug susceptibility testing and PCR-RFLP respectively. The two strains were selected for sequencing procedure. The strain-79 showed point mutation at four points, at codon 70, 71, 76 and 78. The sequence of strain- 81 showed mutation at codon 95.PCR-RFLP is a useful molecular technique for the rapid detection of mutations and may be used to diagnose drug resistance but it should be confirmed by sequencing before starting 2[nd] and 3[rd] generation treatment because the restriction site is the cornerstone of PCR-RFLP and mutation may be occurring elsewhere

Genetic polymorphism of UDP-glucuronosyltransferase [UGT2B15] and glucuronidation of paracetamol in healthy population

Inter individual variability in polymorphic UDP-glucuronosyltransferase [UGT2B15] has been associated with varied glucuronidation level. The present project was designed to determine the genetic polymorphism of UDP-glucuronosyltransferase [UGT2B15] and glucuronidation of paracetamol in healthy [male=59 and female=50] population. The association between genotype [UGT2B15] and phenotype [paracetamol glucuronidation] has been evaluated. According to trimodal model, genotypes and phenotypes were categorized as fast, intermediate and slow glucuronidators. Presence of wild type allele illustrated a UGT2B15 genotype as fast glucuronidator. The glucuronidation status was investigated by HPLC analysis of paracetamol. Ratio of paracetamol glucuronide to paracetamol was determined with two antimodes at glucuronidation ratio of 0.3 and 1.8. In our study, 7% and 12% of population was distributed as slow glucuronidators by phenotype and genotype, respectively and association between phenotype and genotype was good for analysis of glucuronidation status as displayed by kappa value [0.792]

Histopathological evaluation of gastro protective effect of Berberis vulgaris [Zereshk] seeds against aspirin induced ulcer in albino mice

The present study was carried out to investigate the antiulcer activity of Berberis vulgaris [Zereshk] seeds in albino mice. After acclimatization, animals were divided into six equal groups. Aspirin 150mg/kg was used to induce gastric ulcer in all groups except normal control. Omeprazole 20mg/kg was used as synthetic anti ulcer drug in study. Three dose levels of B. vulgaris seed powder 300mg/kg, 600mg/kg and 900 mg/kg were used respectively orally. Histopathological analysis was carried out to evaluate the gastroprotective activity of B. vulgaris seed powder. Results of the study showed that in case of aspirin treated mice gastric luminal mucosa villi were decreased in height or were absent. In the glandular region there was connective tissue proliferation and also infiltration of cells. Similar infiltration of cells was present on muscularis mucosa. In esophageal region tumor cells were present. However three dose levels of B. vulgaris significantly reduced thetissue proliferation, infiltration of cells and sloughing induced by aspirin. Highest dose of B. vulgaris [900mg/kg] showed similar results as synthetic antiulcer drug omeprazole

Cefixime; disposition kinetics and bioavailability comparison of two formulations of cefixime in healthy adult male subjects

Cefixime is a third generation and orally acting cephalosporin. It is a cell wall synthesis inhibitor and is well stable to presence of beta lactamase enzymes. Environmental and genetic differences play a greater role in disposition kinetics of a drug. To determine disposition kinetics of cefixime in local population and to evaluate the bioequivalence of multinational and national brands of cefixime. 2013-2014. Institute of Pharmacy, Physiology and Pharmacology, University of Agriculture, Faisalabad. In present study disposition kinetics and bioequivalence of two brands of cefixime, cefspan and ceforal-3, were investigated in 10 adult healthy male subjects after a single oral dose of 400 mg capsule of each with a 7 days washout period. After blood sampling, plasma concentration of cefixime was determined by HPLC method. For computing disposition kinetic parameters, one compartment open model was applied. Mean values of disposition kinetic parameters; t1/2 Beta 5.01 and 4.72 hours, Vd 1.10 and 1.29 L/kg and CI[B] 0.16 and 0.21 L/hr/kg of cefspan and ceforal-3, respectively, were found non significantly [P 0.05] different. Similarly mean values of bioavailability parameters; AUC 36.58 and 32.99microg.hr/mL, AUMC 282.95 and 264.13 microL/g.hr[2]/mL and MRT 7.79 and 7.83 hours of cefspan and ceforal-3, respectively, remained non significantly [P > 0.05] different. All the parameters were compared by paired t-test. Relative bioavailability was found to be within the range 80-125% which is acceptable for bioequivalence. The test formulation, ceforal-3, was found bioequivalent to the reference formulation, cefspan

Effects of portulaca oleracae [Kulfa] and tarasacum officinale [Dhudhal] in normoglycaemic and alloxan-treated hyperglycemic rabbits

Blood glucose levels of normal and alloxan-diabetic male albino rabbits were determined after oral administration of various doses of the whole, dried and powdered plants of the Portulaca oleracae, Linn. [Fam. Portulacaceae] and Taraxacum officinale, Wiggers [Fam. Compositae]. It was concluded that the powders of both plants produced significant hypoglycaemic effects in normal rabbits but not in alloxan treated rabbits. Acute toxicity and behavioural changes were not observed in the doses tested. It is conceivable that both the indigenous medicinal plants contain some hypoglycaemic principles which act probably by initiating the release of insulin from pancreatic beta-cells of normal rabbits