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Titolo:
Enhanced penetration of indinavir in cerebrospinal fluid and semen after the addition of low-dose ritonavir
Autore:
van Praag, RME; Weverling, GJ; Portegies, P; Jurriaans, S; Zhou, XJ; Turner-Foisy, ML; Sommadossi, JP; Burger, DM; Lange, JMA; Hoetelmans, RMW; Prins, JM;
Indirizzi:
Univ Amsterdam, Acad Med Ctr, Dept Internal Med, Div Infect Dis Trop Med &AIDS,NATEC, NL-1105 AZ Amsterdam, Netherlands Univ Amsterdam Amsterdam Netherlands NL-1105 AZ Z Amsterdam, Netherlands Univ Amsterdam, Acad Med Ctr, Dept Clin Epidemiol & Biostat, NL-1105 AZ Amsterdam, Netherlands Univ Amsterdam Amsterdam Netherlands NL-1105 AZ Z Amsterdam, Netherlands Univ Amsterdam, Acad Med Ctr, Dept Neurol, NL-1105 AZ Amsterdam, Netherlands Univ Amsterdam Amsterdam Netherlands NL-1105 AZ Z Amsterdam, Netherlands Univ Amsterdam, Acad Med Ctr, Dept Human Retrovirol, NL-1105 AZ Amsterdam,Netherlands Univ Amsterdam Amsterdam Netherlands NL-1105 AZ AZ Amsterdam,Netherlands Univ Alabama, Dept Pharmacol & Toxicol, Birmingham, AL USA Univ Alabama Birmingham AL USA t Pharmacol & Toxicol, Birmingham, AL USA Univ Nijmegen, Med Ctr St Radboud, Dept Clin Pharm, Nijmegen, Netherlands Univ Nijmegen Nijmegen Netherlands pt Clin Pharm, Nijmegen, Netherlands Slotervaart Hosp, Dept Pharm & Pharmacol, Amsterdam, Netherlands Slotervaart Hosp Amsterdam Netherlands harmacol, Amsterdam, Netherlands
Titolo Testata:
AIDS
fascicolo: 9, volume: 14, anno: 2000,
pagine: 1187 - 1194
SICI:
0269-9370(20000616)14:9<1187:EPOIIC>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNODEFICIENCY-VIRUS TYPE-1; CENTRAL-NERVOUS-SYSTEM; PERFORMANCE LIQUID-CHROMATOGRAPHY; SEXUAL TRANSMISSION; PHARMACOKINETIC INTERACTION; HIV-1-INFECTED PATIENTS; ULTRAVIOLET DETECTION; PROTEASE INHIBITORS; DRUG CONCENTRATIONS; HIV-1 INFECTION;
Keywords:
indinavir; ritonavir; CSF; semen; pharmacokinetics;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Prins, JM Univ Amsterdam, Acad Med Ctr, Dept Internal Med, Div Infect Dis Trop Med &AIDS,NATEC, Room F4-217,Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands Univ Amsterdam Room F4-217,Meibergdreef 9 Amsterdam Netherlands NL-1105 AZ
Citazione:
R.M.E. van Praag et al., "Enhanced penetration of indinavir in cerebrospinal fluid and semen after the addition of low-dose ritonavir", AIDS, 14(9), 2000, pp. 1187-1194

Abstract

Objective: Penetration of antiretroviral drugs into anatomical HIV-1 reservoirs such as the male genital tract and the central nervous system is important. Data on indinavir (IDV) concentrations in seminal plasma are lackingand IDV concentrations in cerebrospinal fluid are at best borderline. Design: Thirteen patients were treated with zidovudine (or stavudine), lamivudine, abacavir, nevirapine and IDV (1000 mg three times daily). When nevirapine led to low IDV concentrations, IDV was changed into the combinationIDV/ritonavir (RTV) 800/ 100 mg twice daily to improve the pharmacokineticprofile of IDV. Methods: A serum pharmacokinetic profile, a semen sample and a cerebrospinal fluid sample were collected at weeks 8, 24, 48 and 72. Results: Addition of RTV increased the median IDV trough concentration in serum from 65 to 336 ng/ml (P = 0.005). Median IDV concentration in seminalplasma increased from 141 to 1634 ng/ml (P = 0.002) (n = 9) and in cerebrospinal fluid from 39 (n = 12) to 104 (n = 7) ng/ml (P<0.001). In six patients with samples collected both before and after the addition of RTV the IDVconcentration in seminal plasma increased 8.2 times [95% confidence interval (CI) 5.2-11.6], and in cerebrospinal fluid 2.4 times (95% CI 1.8-3.9). Conclusions: IDV penetrates well into the male genital tract. The additionof low-dose RTV not only increases IDV concentrations in serum but also inseminal plasma and cerebrospinal fluid, thereby probably improving the potency of the regimen in these anatomical HIV reservoirs. Higher serum troughlevels alone can not sufficiently explain the observed increases in seminal plasma and cerebrospinal fluid concentrations. Inhibition of P-glycoprotein-mediated transport by RTV might be an additional mechanism. (C) 2000 Lippincott Williams & Wilkins.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 07:25:08