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Biomedical subjects

W D Mason

Publications and source records attributed to W D Mason.

52 records · Page 3Linked to original sources
PubMedDate not supplied

Relative bioavailability of quinidine gluconate and quinidine sulfate in healthy volunteers.

A comparison of the bioavailability of quinidine sulfate to quinidine gluconate tablets in a single-dose randomized cross-over design with 20 healthy volunteers shows that the sulfate salt is more rapidly absorbed and provides significantly greater peak concentrations 1 hour after administration as compared to the peak levels achieved with the gluconate salt at approximately 5 hours after administration. When adjusted for the actual amount of quinidine contained in each tablet, there was no significant difference in the amount of quinidine bioavailable. Since quinidine gluconate absorption is significantly slower than quinidine sulfate, a combination of the two dosage forms may be utilized in providing the loading dose. Based on the computer modeling and the clinical data accumulated by this laboratory (unpublished) over the past four years, quinidine gluconate, in the dosage form utilized in this study, provides more constant blood levels with smaller differences between the Cpmax and Cpmin than the sulfate when administered every 6 or 8 hours. Further controlled clinical studies are needed to confirm these observations in patients.

Adult↗
PubMedDate not supplied

Pharmacokinetics of the anti-AIDS drug 2',3'-dideoxyinosine in the rat.

The pharmacokinetics of 2',3'-dideoxyinosine (ddlno) was examined in the male Fischer 344 rat using reversed phase HPLC with UV and radiochemical detection. Following iv doses of 12, 25, and 100 mg/kg, the parent drug was rapidly eliminated from plasma (mean residence time, 6.3 min; systemic clearance, 64 ml/min/kg). The mean terminal elimination half-life was 28 min and the volume of distribution at steady state was 0.39 liter/kg. Orally administered [3H]ddlno (100 mg/kg) was not significantly bioavailable in the rat, with only 8-11% of the dose absorbed as the parent compound over a 2 hr period. Peak plasma drug concentrations occurred 10 to 20 min following oral administration. Solution stability data suggested that ddlno was unstable at gastric pH (pH 1, t1/2 less than 30 sec). However, elevation of gastric pH with sodium bicarbonate prior to oral administration of ddlno was not effective in increasing the bioavailability of the parent drug. The drug and its metabolic products were extensively distributed into rat tissue 48 hr after iv or oral administration. Following iv infusion of [3H]ddlno to steady state conditions, the highest tissue-to-plasma ratios of radioactivity were found in the kidney (2.2), liver (1.7), and spleen (1.5). Renal clearance accounted for 99% of the eliminated dose. Liver perfusion studies showed that ddlno was not subject to significant hepatic clearance (less than 10%) and that the metabolism was not inducible with phenobarbital.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Pharmacokinetics of codeine after parenteral and oral dosing in the rat.

The pharmacokinetics of codeine was examined in six male Sprague-Dawley rats following iv bolus (3 mg/kg) and oral (5 mg/kg) codeine in a randomized crossover design. Whole blood concentrations of codeine and its O-demethylated metabolite, morphine, were determined by HPLC with electrochemical detection. Following iv codeine administration, the distribution and elimination are best described by an open two-compartment model. The weight normalized volume of distribution of (Vdarea) and total body clearance (CL) were 5.1 +/- 1.7 liters/kg and 6.2 +/- 1.5 liters/kg/hr, respectively. Mean residence time of codeine averaged 34.1 +/- 6.9 minutes. The ratio of AUCmorphine/AUCcodeine was 0.05 +/- 0.02. The absolute bioavailability of codeine calculated was 8.3 +/- 3.2%, indicating extensive first pass metabolism of codeine. An equivalent amount of codeine and morphine were present in the rat following oral codeine. Thus, the amount of morphine formed following codeine administration depends on the route of codeine administration.

Administration, Oral↗
PubMedDate not supplied

Effect of propylene glycol on the disposition of Dramamine in the rabbit.

Dimenhydrinate (Dramamine) is the 8-chlorotheophylline salt of diphenhydramine. Dramamine is commercially available as a solution containing 50 mg dimenhydrinate per ml in 50% propylene glycol/5% benzyl alcohol. Studies in which New Zealand albino female rabbits received dimenhydrinate, i.v. and/or im, revealed evidence of inhibition of drug clearance apparently due to exposure to vehicle. Following im administration of 8-chlorotheophylline to naive rabbits, peak drug levels of 420 ng/ml were attained in 60 min which declined exponentially to near baseline levels within 7 hr. Animals treated with an additional im dose 2 days later achieved blood drug levels of > 2000 ng/ml which were sustained for the duration of the experimental period. Initial i.v. administration of 8-chlorotheophylline resulted in peak concentration of about 5000 ng/ml which declined to near baseline levels within 90 min, while 8-chlorotheophylline (i.v.) blood levels in rabbits exposed to im vehicle (2 days prior) appeared to plateau around 250 ng/ml after 60 min. Acute, short-term exposure to im vehicle did not appear to elicit the altered elimination profiles. An investigation of the influence of the recommended vehicle on the bioavailability and clearance of dimenhydrinate in isolated rabbit liver microsomes revealed that vehicle at concentrations > 0.68 mg/ml significantly decreased the percent of drug metabolized. This effect was directly proportional to the concentration of vehicle added. Studies showed this effect to be due to the propylene glycol component of the vehicle.

Animals↗