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Antimicrobial Agents and Chemotherapy, March 2000, p. 752-755, Vol. 44, No. 3
Department of Infectious Diseases, University
of Genoa, Genoa,1 4th Pediatric Clinic,
University of Milan, Milan,2 and
Virology Laboratory, Istituto Superiore di Sanita',
Rome,3 Italy
Received 4 February 1999/Returned for modification 22 August
1999/Accepted 29 November 1999
The indinavir dosage regimen currently used for human
immunodeficiency virus (HIV)-infected children is not based on
pharmacokinetic data obtained in the target patient population. The
purpose of our study was to characterize indinavir pharmacokinetics and
pharmacodynamics in HIV-infected children. Eleven children (age range,
9.0 to 13.6 years; weight range, 21.7 to 56.0 kg) receiving indinavir
(500 mg/m2 every 8 h) in combination with lamivudine
and stavudine were studied. The correlation of indinavir
pharmacokinetic parameters and demographic parameters was evaluated.
Also, the pharmacodynamic relationship between parameters of indinavir
exposure and parameters of renal toxicity and immunologic recovery was
studied. The area under the indinavir concentration-time curve (AUC)
and patient body surface area (BSA) showed a significant negative
correlation (r = 0.73; P = 0.012). Patients with smaller BSA had excessive indinavir AUC
compared to adults. On the other hand, the median minimum drug
concentration in plasma (Cmin) was lower than
that reported for adults. The maximum indinavir concentration in serum was higher in patients with renal toxicity (5 out of 11 children), but
the difference was not statistically significant (15.3 ± 8.2 versus 9.8 ± 4.4 mg/liter; P = 0.19). There was
a trend toward higher immunologic efficacy in patients with greater
indinavir exposure: the time-averaged AUC of the percentage of
CD4+ lymphocytes over the baseline value for patients with
indinavir Cmin > 95% inhibitory
concentration (IC95) was higher than in patients with
Cmin < IC95
(P = 0.068). Our study suggests that a dose reduction
may be appropriate for children with small BSA and that a 6-h dosage
regimen may be indicated for a substantial percentage of patients. Due
to the low number of patients enrolled in this study, our results
should be confirmed by a larger study.
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Indinavir Pharmacokinetics and Parmacodynamics in
Children with Human Immunodeficiency Virus Infection
*
Corresponding author. Mailing address: Clinica di
Malattie Infettive-Pad 9 F, Ospedale San Martino, Largo R. Benzi 10, 16132 Genova, Italy. Phone: 011-39-10-353 7677. Fax: 011-39-10-353 7680. E-mail: gigatti{at}smartino.ge.it.
Antimicrobial Agents and Chemotherapy, March 2000, p. 752-755, Vol. 44, No. 3
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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