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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Pharmacokinetics and bioavailability of fluconazole in patients with AIDS.

Fluconazole pharmacokinetics were evaluated for 10 volunteers with AIDS who had no clinical evidence of gastroenteritis. Single 100-mg intravenous (i.v.) and oral (p.o.) doses were administered in a randomized, crossover design. i.v. doses were delivered by a constant-rate infusion over 30 min. Serum fluconazole concentrations were measured by gas-liquid chromatography. The i.v. and p.o. studies were modelled simultaneously by iterative two-stage analysis, which provided individual parameter estimates and a population pharmacokinetic model. Median areas under the concentration-time curves for i.v. and p.o. studies did not differ (90.6 and 99.3 micrograms/ml.h, respectively). Consistent with this finding, the median fractional bioavailability was 1.1 (range, 0.45 to 1.3), comparable to those in healthy subjects. Serum pharmacokinetics in these AIDS patients were generally similar to published data for healthy volunteers. However, following p.o. dosing, we observed a slightly delayed and highly variable time to maximum concentration in serum (median, 2 h; range, 15 min to 8 h). Data were well described by a linear, two-compartment pharmacokinetic model with first-order absorption and elimination. Repeated-measures analysis of variance found no significant differences among any of the pharmacokinetic parameters between i.v. and p.o. studies. On the basis of our findings, we suggest no change in dosage of p.o. fluconazole in patients with AIDS who show no clinical signs of enteropathy.[1]

References

  1. Pharmacokinetics and bioavailability of fluconazole in patients with AIDS. DeMuria, D., Forrest, A., Rich, J., Scavone, J.M., Cohen, L.G., Kazanjian, P.H. Antimicrob. Agents Chemother. (1993) [Pubmed]
 
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