Comparative bioavailability of paracetamol.

Prescribing brand name versus generic drugs continues to be a controversial issue. The harmful effects of nonequivalence result from either too little or too much drug reaching the patient which will cause either failure of treatment or adverse drug reactions. On the other hand, if physicians prescribe higher priced original drugs instead of therapeutically equivalent lower cost generic drugs to their patients, the patients then have to pay for the added cost. This study was designed to compare the bioavailability of paracetamol of a generic versus original drug. The original brand (Tylenol, Cilag) which was assigned as the reference standard against another generic formulation (Sara, Thai Nakorn Patana). Ten healthy male volunteers aged 20 to 45 years participated in this study. The study was conducted as a cross-over experimental design. The dose was 2 tablets of 500 mg. In conclusion, based on the concentration-time curve and pharmacokinetic analysis there were no statistically significant differences between T1/2 absorption and Cmax. Although AUC of Sara was marginally statistically greater than Tylenol, this magnitude of difference probably has no clinical significance. All these parameters are within the accepted 20 per cent difference, indicating these products are bioequivalent.

Lead exposure and accumulation in healthy Thais: assessed by lead levels, EDTA mobilization and heme synthesis-related parameters.

Lead is one of the pollutants which is of public concern. The magnitude of lead contamination in Thai people is of interest. The objective of this study was to evaluate the lead status in normal healthy volunteers. Normal volunteers were included. The blood for lead level, Zinc protoporphyrin (ZPP), delta-aminolevulinic acid dehydratase (ALA-D) activity, and baseline urine for lead, delta-aminolevulinic acid (ALA) and coproporphyrinogen III (CP3) were collected. The EDTA mobilization test was done. 24 hour urine after administration of the drug was collected for lead analysis. Thirty volunteers were included in the study. All were men whose average age was 32.5 +/- 6.9 years. The mean lead level was 5.95 +/- 2.01 micrograms/dL and 5.83 +/- 2.32 micrograms/L in urine. The 24 hour urine lead contents before and after EDTA administration were significantly different (11.11 +/- 6.72 and 16.05 +/- 9.51 micrograms respectively). Blood ALA-D activity was 251.6 +/- 80.4 unit/ml of RBC. Urine ALA and CP3 were 0.56 +/- 1.2 mg/L and 22.17 +/- 23.9 micrograms/L respectively. All were in the normal ranges. All parameters suggested that the healthy Thai volunteers had an acceptable magnitude of lead exposure and accumulation.

Risk factors between analgesic use and chronic nephropathy in Thailand.

Analgesic abuse is common in Thailand. Heavy use of analgesic may also increase risk of chronic nephropathy. However, the extent of this risk remains unclear. We carried out a case-control study in three referral hospitals. A total of 84 patients with newly diagnosed of chronic tubulointerstitial nephritis were enrolled as cases. Two control groups were randomly selected, 192 from hospitalized patients who had no renal disease and serum creatinine below 1.2 mg/dl and 166 from relatives of friends visiting the hospitals. Both cases and controls were interviewed by a standardized pre-coded questionnaire to obtain histories of analgesic use before diagnosis of renal disease. On multiple logistic regression analysis, patients whose estimated lifetime use of acetaminophen of 1,000 g or more had an increased risk of chronic nephropathy compared with non-users, the odds ratio (OR) was 5.9 (95% confidence interval (CI) 1.3-25.6, hospital controls) and OR = 5.8 (95% CI 1.04-31.9, visitor controls). Also, uses of aspirin showed a similar relationship. Patients who used aspirin 1,000 g or more per lifetime had higher risk of chronic nephropathy when compared to non-users, the odds ratio were 7.1 (95% CI 2.0-25.8, hospital controls) and 20.4 (95% CI 2.4-174.2) for visitor controls. These data indicate that analgesic abuse increased risk of chronic nephropathy in Thailand.

Acute cyanide poisoning: a case report with toxicokinetic study.

Cyanide poisoning is a life threatening condition. But specific antidotes exist and can be easily prepared from available substances in hospital. Administration of antidotes will produce methemoglobin, which itself causes hypoxia. Nitrite induced methemoglobin can be extremely dangerous and even lethal. Before administering the antidotes, the diagnosis should be confirmed. Nitrite should not be given if the poisoning is mild or diagnosis is uncertain, to avoid excessive methemoglobin, dosage of sodium nitrite must be adjusted according to hemoglobin level (Table 1). Usage of sodium nitrite and sodium thiosulfate in the recommended doses are safe and effective for cyanide poisoning.

Original versus generic piroxicams, their cost-effective evaluation in rheumatoid arthritis (RA) patients.

This was a 12 week double-blind cross over study of 14 patients with rheumatoid arthritis on the cost-effectiveness of different priced piroxicams. All three drugs affected a significant improvement over baseline measurements in most of the clinical parameters assessed with statistical comparable efficacy. Pharmacokinetic analysis also showed similar properties except for the time to reach maximum concentration which was in favor of drug A. This property may be advantageous in treating acute conditions such as gouty attacks. However, in chronic disease like rheumatoid arthritis, there was no significant difference in pharmacologic and clinical efficacy among the three different piroxicams marketed in Thailand.

Bioavailability and pharmacokinetics of furosemide marketed in Thailand.

Thirteen different brands of 40 mg furosemide tablets available in Thailand were evaluated. In vitro studies revealed that all products met the requirement of United States Pharmacopoeia XX for weight variation, per cent labeled amount, and disintegration time. However, there were only 4 brands that passed the dissolution test specification. The original brand (brand A) and the three local brands (brand B, C and D) with differences in dissolution characteristics were selected for bioavailability study. Relative bioavailability of 40 mg furosemide tablets were performed on eight healthy Thai males using a crossover design. Plasma furosemide concentrations were determined by high-performance liquid chromatographic method. Clinical response to these tablets were also studied by determination of urine output and electrolyte excretion. Individual plasma data was analyzed according to one-compartment open model using the PCNONLIN computer program. The elimination half-life of furosemide was 1.27 hours. The mean individual peak plasma levels ranged from 0.61-1.12 micrograms/ml and the time required to reach the peak ranged from 1.63-2.00 hours. There were no statistically significant differences in parameters studied between the original and the local brands (p greater than 0.05). The relative bioavailability of furosemide with respect to brand A were 70.29, 113.41, and 94.93 per cent for brand B, C and D, respectively. There was no relationship between in vitro and in vivo characteristics. Clinical response, in terms of diuresis and electrolyte excretion, e.g., sodium, chloride and potassium, between four brands of furosemide tablets were also not significantly different (p greater than 0.05), indicating that the four brands are clinically equivalent.