Influence of a standard meal on the absorption of a controlled release pseudoephedrine suspension.

The influence of a standard meal on the extent and rate of absorption of pseudoephedrine from a liquid controlled release (CR) formulation (Pennkinetic System) was studied in 16 normal male volunteers. Equivalent single doses of an immediate release reference syrup (IR-Sudafed) and the CR suspension were each studied under both fasted and postprandial conditions. AUC results showed no significant influence of food or formulation, indicating that the CR formulation was absorbed to the same extent as the IR product under all conditions. CMAX and TMAX tabulations under fasted conditions indicated that the CR preparation peaked at a lower level at a later time. Food diminished IR CMAXs but the CR suspension's CMAXs and TMAXs were apparently unaffected by food. This study indicates that this CR pseudoephedrine suspension releases drug independently of food intake.

Bioavailability evaluation of a controlled-release dextromethorphan liquid.

A randomized, two-way, steady-state crossover study was performed in 24 healthy male volunteers to evaluate the bioavailability of a controlled-release (CR) dextromethorphan (DM) suspension. Only slow and intermediate DM metabolizers were allowed to participate in the study; determination of metabolizer status was performed before study enrollment. Each volunteer was administered 30 mg of an immediate-release (IR) DM solution qid or 60 mg DM as a CR suspension bid for two weeks, for a total daily dose of 120 mg. After a two-week washout period, the subjects were administered the alternate treatment. Blood samples were collected over a 12-hour dosing period on the last day of each treatment and analyzed for DM and its active metabolite, dextrorphan (DP). In addition, urine was collected over the 12-hour steady-state dosing interval and measured for DM and two metabolites. Pharmacokinetic determinations were made from plasma DM and DP data, and total urinary excretion was determined. All comparisons made between the two formulations indicated that the CR DM suspension was bioequivalent to the IR DM solution at steady state, while producing a prolonged release of the drug over time.

Influence of a standard meal on the absorption of controlled-release pseudoephedrine capsules.

The influence of a standard meal on the extent and rate of absorption of pseudoephedrine from a controlled-release (CR) capsule formulation (Pennkinetic System) was studied in 16 normal male volunteers. Equivalent single doses of an immediate-release (IR) pseudoephedrine reference syrup and the CR capsules were each studied under both fasted and postprandial conditions. Pharmacokinetic analysis evaluated the fraction of drug absorbed over time as determined by the Wagner-Nelson method. The area under the drug concentration versus time curve (AUC) results were not influenced by food or formulation, indicating that the CR formulation was absorbed to the same extent as the IR syrup. The maximum plasma concentration (Cmax) and the time to maximum concentration (tmax) tabulations under fasted conditions indicated that the CR preparation peaked at a lower level and a later time than the IR syrup. Food minimally affected the Cmax of the IR formulation, but did not affect that of the CR formulation. Food delayed the tmax of both the IR and CR preparations by less than 1 h, but only the delay of the CR formulation was statistically significant. Neither delay was considered clinically meaningful. The results of this study strongly suggest that the pharmacokinetic profile of the CR pseudoephedrine capsules was minimally affected by the presence of food.

Pharmacokinetic evaluation of two doxepin products.

The pharmacokinetics of two marketed formulations of doxepin HCl administered as a single 100-mg oral dose were compared. Sixteen healthy volunteers between the ages of 21 and 50 years participated in this crossover study. A one-week washout period intervened between doses. Blood samples were drawn before drug administration and at various times up to 48 hours after dosing. The concentrations of doxepin (DOX) and desmethyldoxepin (DDOX), the major active metabolite, were determined. Bioequivalence was determined by statistical comparisons of the area under the curve and maximum concentrations of DOX and DDOX. Statistical comparisons indicated no difference between the two formulations with respect to any of the parameters. The results of this study demonstrate that the two formulations of doxepin HCl are bioequivalent and would be expected to have similar clinical efficacy.

Bioavailability assessment of a new liquid controlled-release pseudoephedrine product.

Development of a liquid controlled-release pseudoephedrine product is described. Two bioequivalence studies were conducted. In a single-dose study involving 20 subjects, the bioavailabilities of five controlled-release suspensions with a broad range of drug-release rates were compared with an immediate-release form of pseudoephedrine hydrochloride in a four-way crossover, incomplete block, sequence-randomized study. Serial blood sampling up to 36 hours after drug ingestion provided area-under-the-curve (AUC), maximum plasma concentration (Cmax), and time to peak (tmax). In the multiple-dose study, involving 18 subjects, the bioavailability of the optimal formulation determined from the single-dose study was compared with a reference pseudoephedrine hydrochloride syrup. Serial blood sampling up to 12 hours after drug ingestion was performed to determine AUC, Cmax, and tmax. The single-dose investigation showed that all formulations were bioequivalent except the product with the slowest release rate, which had lower AUC and Cmax values. The results of the multiple-dose study confirmed these findings with the reference syrup. The use of a series of drug formulations with a wide range of release rates permitted selection of an optimal product in addition to providing the information needed to ensure continuous production of bioequivalent products.

Comparison of in vitro activity of undecylenic acid and tolnaftate against athlete's foot fungi.

Undecylenic acid and tolnaftate were tested in an in vitro test system to evaluate their relative "killing time" efficacy against Trichophyton mentagrophytes, Trichophyton rubrum, and Epidermophyton floccosum. Commercial products containing these active agents were tested similarly. The pure active agents were equivalent in activity. The commercial product containing undecylenic acid appeared to be more effective against the test organisms than did the product containing tolnaftate.