Oral bioavailability of griseofulvin from aged griseofulvin:lipid coprecipitates: in vivo studies in rats.
The bioavailabilities of aged coprecipitates of griseofulvin (Gris), dimyristoylphosphatidylcholine (DMPC), or egg phosphatidylcholine (EPC) and cholesterol (CHOL) in rats and correlations with their in vitro dissolution behaviors were determined. In vivo absorption studies of Gris:DMPC (4:1, w/w) or Gris:DMPC:CHOL [4:1(1:0.33 mole ratio)] coprecipitates yielded evidence of a 40% increase in the peak concentration in plasma (Cmax) and a 2.5- to 3-fold decrease in the time to reach Cmax (tmax), compared with those obtained with micronized Gris but a statistically unchanged area under the concentration in plasma--time curve (AUC) when 1-day-aged samples at equivalent doses were used. On the other hand, a 10% decrease in the AUC, a 20% increase in the Cmax, and a three- to fourfold decrease in the tmax were observed for the same formulations aged for 90 days. In comparison, the Cmax produced by the 1-day-aged Gris:EPC:CHOL [4:1(1:0.33 mole ratio)] coprecipitate was the same as that produced by micronized Gris, but the tmax and the AUC were significantly lower; the Cmax produced by the 90-day-aged coprecipitate was 30% higher than that produced by micronized Gris, but the tmax and the AUC remained unchanged. The Gris concentrations after 5 and 30 min (dissolution parameters) and the percent dissolution efficiency also showed excellent correlations with the concentration in plasma after 1 h, the Cmax, and the AUC (in vivo parameters) for all formulations, but the individual in vitro parameters showed poor correlations with the AUC results.(ABSTRACT TRUNCATED AT 250 WORDS)
Vudathala
G K
GK
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Rogers
J A
JA
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002784:Cholesterol / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004134:Dimyristoylphosphatidylcholine / Q000493:pharmacokinetics; D004355:Drug Stability; D006118:Griseofulvin / Q000737:chemistry / Q000493:pharmacokinetics*; D007700:Kinetics; D008055:Lipids / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D010713:Phosphatidylcholines; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013997:Time Factors
D008055:Lipids; D010713:Phosphatidylcholines; D006118:Griseofulvin; D002784:Cholesterol; D004134:Dimyristoylphosphatidylcholine