Abacavir/lamivudine/zidovudine as a combined formulation tablet: bioequivalence compared with each component administered concurrently and the effect of food on absorption.

A single-center, open-label, three-way crossover study was conducted in 24 healthy subjects to assess (1) the bioequivalence of a combined abacavir 300 mg/lamivudine 150 mg/zidovudine 300 mg (A/L/Z) combination tablet relative to the separate brand-name components administered simultaneously and (2) the effect of food on the bioavailability of the drugs from the combination tablet. The subjects were randomly assigned to receive each of the following three treatments, separated by a 2-day washout period: one A/L/Z combination tablet after an overnight fast, one abacavir 300 mg tablet + one lamivudine 150 mg tablet + one zidovudine 300 mg tablet sequentially after an overnight fast, or one A/L/Z combination tablet 5 minutes after completing a standardized high-fat breakfast (67 g fat, 58 g carbohydrate, and 33 g protein). Serial blood samples were collected up to 24 hours postdose for determination of abacavir, lamivudine, and zidovudine serum concentrations. Standard pharmacokinetic parameters were estimated. Treatments were considered bioequivalent if 90% confidence intervals (CI) for geometric least squares (GLS) mean ratios for abacavir, lamivudine, and zidovudine area under the serum concentration-time curve (AUC(infinity)) and maximum observed serum concentration (Cmax) fell entirely within 0.80 to 1.25 for log-transformed parameters. The combined A/L/Z tablet was bioequivalent in the extent (AUC) and rate of absorption (Cmax and time of Cmax [tmax]) to the individual brand-name drug components administered concurrently under fasted conditions. GLS ratios and 90% CI for AUC(infinity) and Cmax were 0.99 (0.96, 1.03) and 1.00 (0.90, 1.11), respectively, for abacavir; 0.95 (0.91, 0.99) and 0.90 (0.84, 0.99), respectively, for lamivudine; and 0.95 (0.89, 1.02) and 0.96 (0.80, 1.15), respectively, for zidovudine. The extent of absorption of abacavir, lamivudine, and zidovudine from the combination tablet was not altered by administration with meals, indicating that this formulation may be administered with or without food. However, food slowed the rate of absorption, delayed the tmax, and reduced the Cmax of abacavir, lamivudine, and zidovudine. These changes, which were consistent with those observed with the individual reference formulations when administered with food, were not considered clinically important. All formulations were well tolerated underfasted and fed conditions.

How is the source of food poisoning outbreaks established? The example of three consecutive Salmonella enteritidis PT4 outbreaks linked to eggs.

Three consecutive outbreaks of Salmonella enteritidis PT4 occurred in Wales in 1989 in which epidemiological and microbiological investigation established eggs as the likely source although kitchen inspection and food preparation histories suggested other vehicles of infection. This paper examines the contribution of analytical epidemiology in attributing causation, with particular reference to those limitations which are regarded as inherent in epidemiological evidence. Such evidence, implicating eggs in the three outbreaks, fulfilled 6/7 widely accepted criteria for causation; data to assess the seventh were lacking. Collaboration between different agencies and professionals in investigating outbreaks is very important.

Pharmacokinetics and safety of lamotrigine (Lamictal) in patients with epilepsy.

In a double-blind parallel study, patients with epilepsy on stable regimen of antiepileptic drugs (AEDs) were given lamotrigine (8 pts) or placebo (3 pts). Patients were sequentially dosed with 100, 200 and 300 mg/day given as a b.i.d. regimen. After steady state was achieved, timed plasma lamotrigine levels were obtained post dose. No medical, psychogenic, neurologic, or hematologic changes were observed and no subjective effects were detected as a result of treatment with lamotrigine. No changes in heart rhythm or blood pressure were observed related to lamotrigine. Pharmacokinetic parameters were calculated using 1-compartment and non-compartment models. The results were similar using both models. Area under the plasma concentration vs. time curves increased linearly with dose. Mean half life (13.5 h), volume of distribution (1.36 l/kg) and clearance (1.27 ml/min/kg) were similar to previously reported results and did not change with increasing dose. These findings indicate that lamotrigine pharmacokinetics can be described by the 1-compartment model, has linear kinetics, and does not induce its own metabolism in patients on concomitant AEDs.

A comparison of the agar gel immuno-diffusion (AGID) and counter-immunoelectrophoresis (CIE) tests for species identification of imported red meat and offal.

From 1 January-31 August, 1984, 585 samples of fresh, uncooked, frozen meat (12) and offal (573) were subjected to the AGID and CIE comparative serological tests for species identification using commercially produced bovine, ovine, porcine and equine anti-species antisera. Species were identified in 286 585 (48·9%) and 581 585 (99·3%) samples by the AGID and CIE tests, respectively. Single species per sample were identified in 246 585 (42·1%) and 481 585 (82·2%) by the AGID and CIE tests. More than one species per sample were identified in 40/585 (6·8%) and 100/585 (17·0%) samples for the same two tests, respectively. The CIE test was more sensitive and rapid in detecting species.

Gas chromatographic analysis of chlorophenylmercapturic acid lindane metabolites.

An analytical method for phenols has been adapted for the analysis of chlorophenylmercapturic acids in rat urine. Chlorothiophenols were produced from the mercapturic acids by hydrolytic cleavage with sodium hydroxide. Acetate esters of the chlorothiophenols were formed by addition of acetic anhydride to the aqueous alkaline solution. After acylation, the acetate derivatives were extracted into hexane. Forming the acetate esters of the chlorothiophenols prevented their oxidation to disulfides and significantly improved their chromatographic properties. Electron-capture gas chromatographic analysis of the stable acetate esters was performed on a mixed phase column, 4% SE-30 + 6% OV-210. Recoveries of four chlorothiophenols ranged from 82 to 93%. This method required no sample transfer steps; therefore, sample loss and analysis time were minimized.

Recent developments in air transportation of farm animals and horses.

This paper deals with some recent developments in the air transportation of cattle, sheep, pigs and horses and comments on the factors involved which influence the results.