Renal excretion and pharmacokinetics of foscarnet in HIV sero-positive patients: effect of probenecid pretreatment. 1997

F H Noormohamed, and M S Youle, and C J Higgs, and B G Gazzard, and A F Lant
Department of Therapeutics, Charing Cross and Westminster Medical School, Chelsea and Westminster Hospital, London, UK.

OBJECTIVE 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.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011339 Probenecid The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. Benecid,Benemid,Benuryl,Pro-Cid,Probecid,Probenecid Weimer
D012076 Renal Agents Drugs used for their effects on the kidneys' regulation of body fluid composition and volume. The most commonly used are the diuretics. Also included are drugs used for their antidiuretic and uricosuric actions, for their effects on the kidneys' clearance of other drugs, and for diagnosis of renal function. Agents, Renal
D006679 HIV Seropositivity Development of neutralizing antibodies in individuals who have been exposed to the human immunodeficiency virus (HIV/HTLV-III/LAV). AIDS Seroconversion,AIDS Seropositivity,Anti-HIV Positivity,HIV Antibody Positivity,HIV Seroconversion,HTLV-III Seroconversion,HTLV-III Seropositivity,AIDS Seroconversions,AIDS Seropositivities,Anti HIV Positivity,Anti-HIV Positivities,Antibody Positivities, HIV,Antibody Positivity, HIV,HIV Antibody Positivities,HIV Seroconversions,HIV Seropositivities,HTLV III Seroconversion,HTLV III Seropositivity,HTLV-III Seroconversions,HTLV-III Seropositivities,Positivities, Anti-HIV,Positivities, HIV Antibody,Positivity, Anti-HIV,Positivity, HIV Antibody,Seroconversion, AIDS,Seroconversion, HIV,Seroconversion, HTLV-III,Seroconversions, AIDS,Seroconversions, HIV,Seroconversions, HTLV-III,Seropositivities, AIDS,Seropositivities, HIV,Seropositivities, HTLV-III,Seropositivity, AIDS,Seropositivity, HIV,Seropositivity, HTLV-III
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D017245 Foscarnet An antiviral agent used in the treatment of cytomegalovirus retinitis. Foscarnet also shows activity against human herpesviruses and HIV. Phosphonoformate,Phosphonoformic Acid,Foscarnet Barium (2:3) Salt,Foscarnet Calcium (2:3) Salt,Foscarnet Disodium Salt,Foscarnet Magnesium (2:3) Salt,Foscarnet Manganese (2+) (2:3) Salt,Foscarnet Sodium,Foscarnet Sodium Hexahydrate,Foscarnet Trilithium Salt,Foscarnet Tripotassium Salt,Foscarnet Trisodium Salt,Foscavir,Trisodium Phosphonoformate

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