Bioavailability of immediate- and extended-release formulations of glipizide in healthy male volunteers.

BACKGROUND AND OBJECTIVE: An extended-release glipizide formulation using a hydrophilic matrix system containing hydrophilic polymers has been developed for use in diabetes mellitus. This study compared the pharmacokinetic parameters of immediate- and extended-release formulations of glipizide 5mg in healthy male volunteers. METHODS: In a single-dose, four-period, four-treatment, Latin-square crossover study, the bioavailability of immediate-release glipizide 5mg (Glynase) [GL], extended-release glipizide 5mg (Glynase) XL [GLXL], Glucotrol XL [GTXL], and the new formulation developed in our laboratory [GLPF]) was compared. Plasma glipizide levels of the four formulations were determined at different time intervals, and pharmacokinetic parameters were analysed using a two-compartment body model. RESULTS: The mean peak plasma concentration (C(max)) of the immediate-release formulation (523+/-60 ng/mL) was significantly higher (p<0.05) than those of the three extended-release formulations (403+/-24, 349+/-37 and 426+/-55 ng/mL for GLXL, GTXL and GLPF, respectively). Mean time to reach C(max) was 1.83+/-0.3 hours for GL, 4.41+/-1.2 hours for GLXL, 3.21+/-0.8 hours for GTXL and 3.24+/-0.4 hours for GLPF. The order of magnitude of area under the plasma concentration-time curve was GTXL (5591 ng . h/mL)>GLXL (4,771 ng . h/mL)>GLPF (4,537 ng . h/mL)>GL (1,897 ng . h/mL). The mean residence time was 3.14+/-0.59 hours for GL, 8.26+/-0.81 hours for GLXL, 9.70+/-2.70 hours for GTXL and 7.87+/-1.93 hours for GLPF. Extended-release glipizide formulations maintained effective plasma drug concentrations for approximately 24 hours. Plasma levels of glipizide fluctuated less with GTXL than with the other two extended-release formulations. CONCLUSION: The newly developed formulation (GLPF) maintained effective levels of glipizide for a period of more than 20 hours, with quicker onset of action than the other two formulations. This formulation may be more economical than glipizide GITS.

Pharmacokinetics of oral ibuprofen in premature infants.

Patent ductus arteriosus (PDA) is a frequent complication in premature infants. So far, intravenous indomethacin is the standard mode of medical therapy in such patients but carries a risk of frequently occurring side effects. Ibuprofen, another nonsteroidal anti-inflammatory drug, has also been shown to be efficacious in closing ductus with lesser adverse effects after parenteral administration. However, limited data are available on the pharmacokinetics of intravenous ibuprofen in this population. Nonavailability of parenteral preparation and lack of information regarding pharmacokinetic disposition of ibuprofen in this subgroup of the population led the authors to conduct this pharmacokinetic study with oral ibuprofen. Twenty premature infants with a gestational age of 30.45 +/- 0.33 weeks and a birth weight of 1262.5 +/- 55.4 g (values given as mean +/- SEM) admitted to the neonatal unit were enrolled in this study. Ibuprofen was administered in a single oral dose of 10 mg/kg between 4 and 72 hours postnatally, and blood samples were collected through an indwelling vascular catheter at time 0 and 1, 2, 4, 8, 12, and 24 hours. Ibuprofen plasma concentrations were assayed by high-performance liquid chromatography. There was a large interindividual variability observed for plasma concentrations, elimination half-life (t1/2) (15.72 +/- 3.76 h), and area under the plasma concentration-time curve (AUC0-infinity) (402.60 +/- 79.67 micrograms.h/mL) in these babies. Variables such as gestational age, birth weight, and sex did not affect ibuprofen pharmacokinetics significantly (p > 0.05). Moreover, no correlation could be found between elimination half-life and gestational age (r = 0.02). Ibuprofen pharmacokinetics showed a wide variability in premature infants. The results of the present study warrant revising the oral dosage schedule to achieve comparable plasma concentrations of ibuprofen associated with successful closure of ductus, as reported in earlier studies.