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Titolo:
ABSORPTION AND ELIMINATION KINETICS OF ZIDOVUDINE IN THE CEREBROSPINAL-FLUID IN HIV-1-INFECTED PATIENTS
Autore:
ROLINSKI B; BOGNER JR; SADRI I; WINTERGERST U; GOEBEL FD;
Indirizzi:
UNIV CHILDRENS HOSP,LINDWURMSTR 4 D-80337 MUNICH GERMANY UNIV MUNICH,DEPT INTERNAL MED MUNICH GERMANY UNIV MUNICH,DEPT PEDIAT MUNICH GERMANY
Titolo Testata:
Journal of acquired immune deficiency syndromes and human retrovirology
fascicolo: 3, volume: 15, anno: 1997,
pagine: 192 - 197
SICI:
1077-9450(1997)15:3<192:AAEKOZ>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
AIDS DEMENTIA COMPLEX; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; NEUROLOGICAL DISEASE; CONTROLLED TRIAL; HIV-INFECTION; 3'-AZIDO-3'-DEOXYTHYMIDINE; PHARMACOKINETICS; THERAPY; AZT; 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE;
Keywords:
ZIDOVUDINE (ZDV); CEREBROSPINAL FLUID (CSF); CENTRAL NERVOUS SYSTEM (CNS); ANALYSIS; PHARMACOKINETICS; BLOOD-CSF BARRIER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
25
Recensione:
Indirizzi per estratti:
Citazione:
B. Rolinski et al., "ABSORPTION AND ELIMINATION KINETICS OF ZIDOVUDINE IN THE CEREBROSPINAL-FLUID IN HIV-1-INFECTED PATIENTS", Journal of acquired immune deficiency syndromes and human retrovirology, 15(3), 1997, pp. 192-197

Abstract

Current knowledge of zidovudine (ZDV) levels in human cerebrospinal fluid (CSF) is limited to single sample determination and extrapolationto time after administration. Longitudinal studies have not been performed. Pharmacokinetic parameters of ZDV in CSF were determined in sixHIV-1-infected patients. CSF samples were collected by an intraspinalcatheter over a period of 6 hours after a single intravenous (IV) dose of ZDV (2.5 mg/kg). ZDV concentrations were measured by high-performance liquid chromatography (HPLC). ZDV was cleared rapidly from plasma, with a mean terminal elimination half-life (t(1/2)) of 75.5 +/- 4.9 minutes, ZDV penetrated slowly into the CSF, reaching maximal concentration (Cmax) 2 hours after the start of the infusion in all patients. ZDV was cleared from the CSF with a mean t(1/2) of 187.6 +/- 69.3 minutes. Mean Cmax in the CSF was 1.3 +/- 1.2 mu mol/l (17% of that of plasma), and mean area under the concentration time curve (AUC) was 358 +/- 200 mu mol.minutes/l (75% of that of plasma). There was a significant correlation between plasma and CSF for Cmax (r=0.88, p=.009) and AUC (r=0.89, p=.014). Calculated trough levels in CSF for a 12-hour dosing interval were 0.090 +/- 0.065 mu mol/l and thus about twice the 50%inhibitory concentration (IC50) of susceptible HIV strains. The CSF-plasma ratio of ZDV increased in a nearly linear fashion with time after drug administration. Thus, ZDV has a distinct pharmacokinetic profile in CSF compared with other compartments of the body.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 12:33:41