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Vol. 83, No. 1, 2009
Issue release date: December 2008
Section title: Original Paper
Pharmacology 2009;83:59–66
(DOI:10.1159/000178813)

Pharmacokinetic Study of the Variability of Indinavir Drug Levels when Boosted with Ritonavir in HIV-Infected Children

Curras V. · Höcht C. · Mangano A. · Niselman V. · Mariño Hernández E. · Cáceres Guido P. · Mecikovsky D. · Bellusci C. · Bologna R. · Sen L. · Rubio M.C. · Bramuglia G.F.
Cátedras deaFarmacología y bMatemática, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, y cArea de Farmacia, dServicio de Control Epidemiológico e Infectología y eLaboratorio de Biología Celular y Retrovirus, Hospital de Pediatría Juan P. Garrahan, Buenos Aires, Argentina; fUnidad de Farmacia Clínica y Farmacoterapia, Facultad de Farmacia, Universidad de Barcelona, Barcelona, España

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 6/18/2008
Accepted: 8/19/2008
Published online: 12/4/2008

Number of Print Pages: 8
Number of Figures: 2
Number of Tables: 2

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: http://www.karger.com/PHA

Abstract

The aim of this work is to: (1) assess therapeutic drug monitoring of indinavir (IDV) during clinical routine practice in HIV-infected children, whose antiretroviral treatment includes IDV boosted with ritonavir (RTV), and (2) describe a possible relationship between IDV pharmacokinetics and MDR1 genotypes. In 21 ambulatory pediatric patients receiving IDV plus RTV, IDV plasma levels and MDR1 genotypes on exon 26 (C3435T) were determined. Nine of the 21 patients initially receiving 250 mg/m2 IDV yielded trough levels below 0.10 μg/ml (median: 0.21, range: 0.04–1.31 μg/ml). When the dosage was increased to 400 mg/m2 IDV plus 100 mg/m2 RTV b.i.d., all, except 1 patient, achieved levels above 0.10 μg/ml. Pharmacokinetic analysis showed higher volume of distribution median values related to the C/C genotype in comparison with C/T or T/T genotypes for exon 26 (4.57 vs. 1.20 and 1.50 l/kg, respectively; p = 0.002). Although a higher median value of clearance was observed with the C/C genotype, the difference was not statistically significant (1.43 vs. 0.27 and 0.42 l/h, respectively; p = 0.052). These results may be explained by a reduced absorption of the drug, related with lower plasma IDV levels in patients carrying the C/C genotype in exon 26.


  

Author Contacts

Guillermo F. Bramuglia
Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, UBA
Junin 956 5th floor (C1113AAD)
Buenos Aires (Argentina)
Tel. +54 11 49 648 265, Fax +54 11 45 083 645, E-Mail gbram@ffyb.uba.ar

  

Article Information

Received: June 18, 2008
Accepted: August 19, 2008
Published online: December 4, 2008
Number of Print Pages : 8
Number of Figures : 2, Number of Tables : 2, Number of References : 38

  

Publication Details

Pharmacology (International Journal of Experimental and Clinical Pharmacology)

Vol. 83, No. 1, Year 2009 (Cover Date: December 2008)

Journal Editor: Donnerer J. (Graz), Billingsley M.L. (Hershey, Pa.), Maeyama K. (Matsuyama)
ISSN: 0031–7012 (Print), eISSN: 1423–0313 (Online)

For additional information: http://www.karger.com/PHA


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 6/18/2008
Accepted: 8/19/2008
Published online: 12/4/2008

Number of Print Pages: 8
Number of Figures: 2
Number of Tables: 2

ISSN: 0031-7012 (Print)
eISSN: 1423-0313 (Online)

For additional information: http://www.karger.com/PHA


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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