AIMS: The present study was undertaken to test whether the anti-viral agent foscarnet undergoes significant 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 microM (foscarnet) and 862 +/- 97 microM (foscarnet+probenecid) whilst the plasma AUC values were 3326 +/- 451 microM h and 3133 +/- 476 microM 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 (foscarnet) and 25 +/- 31 (foscarnet+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. CONCLUSIONS: 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.
AIMS: The present study was undertaken to test whether the anti-viral agent foscarnet undergoes significant 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 seropositivepatients. RESULTS: Mean (+/-s.d.) peak plasma concentrations were 904 +/- 65 microM (foscarnet) and 862 +/- 97 microM (foscarnet+probenecid) whilst the plasma AUC values were 3326 +/- 451 microM h and 3133 +/- 476 microM 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 (foscarnet) and 25 +/- 31 (foscarnet+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. CONCLUSIONS: 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.
Authors: F H Noormohamed; M S Youle; C J Higgs; S Martin-Munley; B G Gazzard; A F Lant Journal: Antimicrob Agents Chemother Date: 1998-02 Impact factor: 5.191