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Renal excretion and pharmacokinetics of foscarnet in HIV sero‐positive patients: effect of probenecid pretreatment
Author(s) -
Noonnohamed F. H.,
Youle M. S.,
Higgs C. J.,
Gazzard B. G.,
Lant A. F.
Publication year - 1997
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1997.tb00147.x
Subject(s) - foscarnet , probenecid , pharmacokinetics , pharmacology , chemistry , renal function , creatinine , medicine , urology , ganciclovir , human cytomegalovirus , biochemistry , gene
Aims The present study was undertaken to test whether the anti‐viral agent foscarnet undergoes sipficant tubular secretion, by using probenecid, an inhibitor of the organic acid secretory pathway in the proximal segment of the nephron. Methods The pharmacokinetics and renal excretion of foscarnet (90 mg kg −1 infused over 2 h) have been investigated, in the absence and presence of probenecid pretreatment (1 g twice daily for 3 days) in a group of 10 HIV seropositive patients. Results Mean (± s.d.) peak plasma concentrations were 904 ± 65 μm (foscarnet) and 862 ± 97 μm (foscarnet + probenecid) whilst the plasma AUC values were 3326 ± 451 μm h and 3133 ± 476 μm h respectively. Terminal elimination half‐life remained unchanged at 5.6 ± 0.7 h and the respective volumes of distribution at steady state were 23 ± 31 (foscamet) and 25 ± 31 (foscamet + probenecid). Mean total body clearance was 110 ± 17 ml min −1 (foscarnet) and 113 ± 13 ml min −1 (foscarnet + probenecid) and the corresponding renal clearances of foscarnet were 102 ± 5 ml min −1 and 105 ± 5 ml min −1 respectively. There were no significant differences in the total amount of foscarnet excreted by the kidney with 95 ± 5% (foscarnet) and 91± 6% (foscarnet + probenecid) of the intravenous dose excreted within 24 h. Glomerular filtration rates at 109 ± 12 ml min −1 (foscarnet) and 100 ± 13 ml min −1 (foscarnet + probenecid) and respective creatinine clearances at 120 ±15 and 119 ± 10 ml min −1 remained unchanged throughout the study. Conclusion The study shows that foscarnet is not transported via the probenecid‐sensitive organic acid secretory pathway in the proximal tubule; the renal elimination of foscarnet is via glomerular filtration.