Relative bioavailability of griseofulvin lyophilized dry emulsion tablet vs. immediate release tablet: a single-dose, randomized, open-label, six-period, crossover study in healthy adult volunteers in the fasted and fed states.

The oral bioavailability of griseofulvin (GF) formulated as a fast disintegrating lyophilized dry emulsion (LDE) tablet was studied and compared to the commercially available immediate release (IR) tablet, as a reference, in both the fasted and fed states in nine healthy volunteers after a single oral dose (125 mg) in a crossover design. Furthermore the LDE tablets were ingested with and without water under both the fasted and fed states. In the fasted state, the rate of absorption was found to be significantly faster from LDE tablets, in the presence and absence of water, as shown by a higher C(max) (more than two times higher, p=0.0001) and a shorter t(max) (by more than 3h, p=0.0001) compared to IR tablets. The extent of absorption, expressed as AUC, from LDE tablets in the presence and absence of water was 65% and 77% larger and statistically significantly different relative to the mean AUC from IR tablets (p=0.006). In the fed state, C(max) from LDE tablets ingested with and without water was found to be about 30% and 50% higher, respectively, than the immediate release tablets. A shorter t(max) was also shown whether LDE tablets were ingested with or without water in the fed state as compared to immediate release tablets. The mean AUC from LDE tablets under fed conditions in the presence of water was about 21% larger and was not statistically significantly different from AUC from immediate release tablets (p=0.517). When ingested without water, AUC from LDE tablets was about 43% larger and statistically significantly different relative to AUC from IR tablets (p=0.033). The mean AUC from the LDE tablet ingested with water under fed conditions relative to AUC from LDE tablet ingested without water was not statistically significantly different (p=0.454). Results show that the food effect of the high fat meal is very pronounced in case of the immediate release tablets, Fulvin, than in case of LDE tablets whether given with or without water.

Administration of tobramycin in the beginning of the hemodialysis session: a novel intradialytic dosing regimen.

BACKGROUND: Aminoglycoside antibiotic efficacy is related to peak concentration (C(max)) and postantibiotic effect, whereas toxicity is directly related to body exposure as measured by area under the serum concentration versus time curve (AUC). On the basis of pharmacokinetic simulation models, tobramycin administration during the first 30 min of high-flux hemodialysis achieves similar C(max) but significantly lower AUC and prehemodialysis concentrations compared with conventional dosing in the last 30 min of hemodialysis. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: To test this hypothesis, a pilot study in which five adult chronic hemodialysis patients who were undergoing high-flux dialysis received one dose of tobramycin 1.5 mg/kg intravenously during the first or last 30 min of hemodialysis was conducted. After a 1-mo washout period, patients crossed over to the other treatment schedule. Tobramycin serum concentrations were measured to determine C(max), interdialytic and intradialytic elimination rate constants and half-lives, AUC, and clearance. RESULTS: Tobramycin administration during the first and last 30 min of hemodialysis resulted in similar C(max) of 5.63 +/- 0.49 and 5.83 +/- 0.67 mg/L (P > 0.05) but significantly lower prehemodialysis concentrations of 0.16 +/- 0.09 and 2.44 +/- 0.43 mg/L (P < 0.001) and AUC of 21.06 and 179.23 +/- 25.84 mg/h per L (P < 0.001), respectively. CONCLUSIONS: Tobramycin administration during the first 30 min of hemodialysis results in similar C(max) but lower AUC to conventional dosing, which may translate into comparable efficacy but lower toxicity.