The influence of food on itraconazole pharmacokinetics was evaluated for 27 healthy male volunteers in a single-dose (200 mg) crossover study with capsules containing itraconazole-coated sugar spheres. This study was followed by a study of the steady-state pharmacokinetics for the same subjects with 15 days of administration of itraconazole at 200 mg every 12 h. Concentrations of itraconazole and hydroxyitraconazole, the active main metabolite, were measured in plasma by high-performance liquid chromatography. The results of the food interaction segment showed that a meal significantly enhances the amount of itraconazole absorbed. The mean maximum concentration in plasma of unmetabolized itraconazole after fasting (140 ng/ml) was about 59%o that after the standard meal (239 ng/ml). The rate of elimination was not affected (terminal half-life, approximately 21 h). The mean maximum concentration in plasma of hydroxyitraconazole after fasting was about 72% the postmeal concentration (287 and 397 ng/ml, respectively). The terminal half-life of hydroxyitraconazole was approximately 12 h. Steady-state concentrations of itraconazole and hydroxyitraconazole were reached after 14 or 15 days of daily dosing. The average steady-state concentrations were approximately 1,900 ng/ml for itraconazole and 3,200 ng/ml for hydroxyitraconazole. The shape of the elimination curve for itraconazole after the last dose was indicative of saturable elimination. This conclusion was confirmed by the sevenfold increase in the area under the curve from 0 to 12 h at steady state compared with the area under the curve from 0 h to infinity after a single dose. It was furthermore confirmed by the larger-than-expected number of half-lives required to achieve steady-state plasma drug levels.

The bioavailabilities and bioequivalences of single 200-mg doses of itraconazole solution and two capsule formulations were evaluated in a crossover study of 30 male volunteers. The two capsule formulations were bioequivalent. The bioavailabilities of the solutions itraconazole and hydroxyitraconazole were 30 to 33% and 35 to 37% greater, respectively, than those of either capsule. However, the maximum concentrations of the drug in plasma (C max), the times to C max, and the terminal half-lives were comparable for all three formulations. These data indicate that the bioavailabilities of itraconazole and hydroxyitraconazole are enhanced when administered as an oral solution instead of capsules.

Ketoconazole is an orally effective, broad-spectrum, systemic antifungal agent. The pharmacokinetics and bioavailability of ketoconazole given as a 200-mg single dose in a tablet, suspension, or solution were studied in 24 fasting healthy males by using a crossover design. Levels of ketoconazole in plasma were determined for up to 48 h by a sensitive reverse-phase high-performance liquid chromatography method. The absorption of ketoconazole was rapid, with mean maximum concentrations of the drug in plasma of 4.2, 5.0, and 6.2 ,g/ml attained at 1.7, 1.2, and 1.0 h, respectively, after administration of the tablet, suspension, and solution, respectively. The mean distribution and elimination half-life values were 1.5 to 1.7 and 7.5 to 7.9 h, respectively. The mean oral clearance of the solution dose was 209 (+82.9 [standard deviation]) ml/min, and the mean apparent volume of distribution was 88.31 (±68.72) liters. The relative bioavailabilities for the tablet and suspension were 81.2 (±33.5) and 89.0 (±23.1)%, respectively, of that of the solution. The data indicated the bioequivalence of the tablet to the suspension and of the suspension to the solution. Dose proportionality of ketoconazole was also studied in 12 volunteers after they received solution doses of 200, 400, and 800 mg. Linear correlations between the dose and the maximum concentration of the drug in plasma, the time to the maximum concentration, and the area under the concentration-time curve were observed. However, the increase in the area under the curve was more than proportional to the dose given. The levels in plasma seemed to decay at a lower rate after 400-and 800-mg doses. The mean oral clearance decreased from 244.9 to 123.6 and 80.0 ml/min, respectively, as the dose increased from 200 to 400 and 800 mg. The apparent dose-dependent kinetics may have been due to the presystemic elimination and capacity-limited hepatic metabolism which become saturated at higher doses.Ketoconazole is a synthetic imidazole-dioxolane derivative with a broad spectrum of antifungal activity. Although its spectrum of activity is similar to those of other imidazole derivatives, e.g., miconazole, econazole, and clotrimazole, ketoconazole has the advantage of being effective when administered orally. Its therapeutic efficacy was reviewed recently (7). After a 200-mg tablet dose to healthy subjects, peak ketoconazole concentrations in plasma (Cmax) of 3 to 4.5 ,ug/ml were reached within 1 to 2 h and the therapeutic activity was maintained for several hours after administration of the drug (8). The recommended dosage for ketoconazole is 200 mg daily. In serious infections, higher doses may be required. Ketoconazole is available as a 200-mg tablet (10).The objectives of this study were (i) to determine the bioavailabilities of the ketoconazole tablet and an experimental suspension formulation relative to a reference aqueous solution and (ii) to evaluate in healthy, male volunteers the dose proportionality of ketoconazole in doses ranging from 200 to 800 mg. MATERIALS AM...

No abstract

Telepharmacy is a rapidly growing area of communication within pharmaceutical care delivery, especially in rural areas. The purpose of this literature review is to determine how telepharmacy is currently being practiced within community and ambulatory pharmacy settings, its effectiveness, and how it is being regulated across the United States. A literature review was performed using PubMed, Ovid MEDLINE, and the Google search engine. State-specific rules were researched using board of pharmacy and legislative online resources. Telepharmacy has been successfully implemented within community pharmacy settings through the creation of remote dispensing sites. The increasing focus of state regulations on telepharmacy services and practices shows the growth and acceptance of this modality of pharmacy practice. There is wide variation among state regulations pertaining to the setup and operation of telepharmacies. Trends in telemedicine show that telepharmaceutical care is likely to continue to expand as it allows for a better allocation of resources and access to more patients. However, research needs to be conducted to specifically analyze the value and place for telepharmacy services.