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A W Kinkel

Publications and source records attributed to A W Kinkel.

29 records · Page 2Linked to original sources
PubMedDate not supplied

Bioavailability of propranolol hydrochloride tablet formulations: application of multiple dose crossover studies.

Two multiple dose crossover pharmacokinetic studies were carried out to determine the steady-state bioavailability of newly formulated generic propranolol HCl tablets relative to Inderal tablets. In Study I, 24 healthy volunteers were dosed with 4 x 10 mg test tablets, 1 x 40 mg test tablet, 4 x 10 mg Inderal tablets, and 40 mg of propranolol HCl in solution. In Study II, 24 healthy volunteers were dosed with 1 x 80 mg test tablet, 1 x 80 mg Inderal tablet, and 80 mg of propranolol HCl in solution. Both studies were of randomized design with each formulation administered every 8 h for 15 doses. Serial plasma samples were obtained for 8 h after morning doses on Days 4 and 5 of each treatment period and assayed for propranolol using a validated HPLC method. Mean plasma concentration-time data for test tablets and reference tablets were superimposable in both studies. Pharmacokinetic parameters from Days 4 and 5 were combined for statistical analysis since subjects were determined to have reached steady-state. Mean AUC, Cmax, tmax, and Cmin values were not statistically different between test tablets and Inderal tablets in either study. Based on these findings, the test tablets demonstrated the same rate and extent of propranolol absorption as did corresponding Inderal tablets. Therefore, the test tablets and Inderal tablets were determined to be bioequivalent.

Biological Availability↗
PubMedDate not supplied

A single and multiple dose pharmacokinetic and metabolism study of meclofenamate sodium.

A single and multiple oral dose administration study of meclofenamate sodium (Meclomen) was conducted in ten healthy male volunteers. An initial 300 mg oral dose on day 1 was followed by a 100 mg every 8 h dosage regimen on study days 4 through 18. Intensive plasma and urine sample collection was carried out over the first three study days, and for 120 h following administration of the final dose on day 18. Plasma and urine specimens were analyzed by a specific HPLC assay for unconjugated meclofenamic acid and metabolites I and II of meclofenamic acid before and after sample incubation with beta-glucuronidase. Meclofenamic acid was rapidly absorbed following oral dose administration. Concentrations of meclofenamic acid existed primarily as unconjugated drug in plasma, with only a small amount present in the conjugated form. Meclofenamic acid was rapidly eliminated, with an elimination half-life of approximately 1.3 h. This resulted in no detectable accumulation upon multiple dose administration. Metabolite I, which is one-fifth as active as meclofenamic acid in in vitro inhibition of cyclooxygenase, was present in unconjugated form at steady state in concentrations approximately 50 per cent of those of meclofenamic acid, as unconjugated drug. The majority of metabolite I in plasma existed as glucuronide conjugate. Metabolite II, which is inactive, was present in very significant concentrations in unconjugated form. Plasma protein binding determinations conducted on meclofenamic acid and metabolite I indicated that the free fraction of metabolite I was 8.7 to 10.9 times higher than that of meclofenamic acid. When the lower activity and lower steady state concentrations, but higher free fraction, are considered, it would appear that metabolite I may contribute significantly to the in vivo inhibition of cyclooxygenase activity seen after administration of meclofenamic acid.

Adult↗
PubMedDate not supplied

Pharmacokinetic profile of a 300-mg extended phenytoin sodium capsule (Dilantin) formulation.

The pharmacokinetic profile of a newly developed Dilantin 300-mg Kapseal formulation was compared with that of currently marketed Dilantin 100-mg Kapseals in both a 300-mg single-dose bioequivalence study in nine healthy volunteers and a once-daily 300-mg multiple-dose study in 18 patients with seizures. Results of these studies indicate the rate and extent of absorption of the 300-mg extended phenytoin (PHT) sodium capsule formulation are similar to that of 100-mg extended PHT sodium capsules based on PHT plasma maximum concentrations and time to achieve them (Cmax, tmax), and area under the curve (AUC) values and the urinary excretion of total hydroxy phenylhydantoin (HPPH) in the single-dose study and steady-state PHT plasma Cmax, tmax, minimum plasma concentrations (Cmin), and AUC values and urinary excretion of total HPPH in the multiple-dose study. Control of seizures in patients was equally maintained on a once-daily 300-mg multiple-dosing regimen administered as either one 300-mg extended PHT sodium capsule daily or three 100-mg extended PHT sodium capsules daily. Therefore, 300-mg extended PHT sodium capsules can be safely and effectively interchanged with three 100-mg extended PHT sodium capsules in patients requiring a once-daily 300-mg PHT sodium dosing regimen.

Adult↗