International Journal of STD & AIDS > Volume 18, Number 2 > Pp. 81-84

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Original research articles

Dose reduction effective in alleviating symptoms of saquinavir toxicity

C Stephan, A Carlebach, C Rottmann, A Haberl, B Dauer, N von Hentig, M Kurowski and S Staszewski

Medical HIV Treatment and Research Unit, Hospital of the Johann Wolfgang Goethe University, Department of Internal Medicine II, Frankfurt, Germany; Medical HIV Treatment and Research Unit, Hospital of the Johann Wolfgang Goethe University, Department of Internal Medicine II, Frankfurt, Germany; Medical HIV Treatment and Research Unit, Hospital of the Johann Wolfgang Goethe University, Department of Internal Medicine II, Frankfurt, Germany; Medical HIV Treatment and Research Unit, Hospital of the Johann Wolfgang Goethe University, Department of Internal Medicine II, Frankfurt, Germany; Medical HIV Treatment and Research Unit, Hospital of the Johann Wolfgang Goethe University, Department of Internal Medicine II, Frankfurt, Germany; Pharma Center Frankfurt at Johann Wolfgang Goethe-University, Institute of Clinical Pharmacology, Frankfur; Auguste-Viktoria Hospital, HIV-LAB, Berlin, Germany; Medical HIV Treatment and Research Unit, Hospital of the Johann Wolfgang Goethe University, Department of Internal Medicine II, Frankfurt, Germany

Gastrointestinal intolerance is a limitation of boosted saquinavir antiretroviral treatment. We present three HIV-infected individuals whose severe toxicity symptoms started directly after initiation of a standard dose saquinavir hard-gel capsule-containing regimen (saquinavir/ritonavir 1000/100 mg). All patients underwent immediate 12 h pharmacokinetic (PK) assessment and showed extraordinarily high saquinavir plasma exposure. All three patients did not recover until the saquinavir exposure was decreased. This pilot case study anticipates a new concept of 'direct PK'-guided individual dose interventions under close viral load monitoring. Two major reasons for symptomatic saquinavir overexposure were defined: impaired liver function in a chronic hepatitis C virus co-infected individual at normal liver performance parameters and a delayed cytochrome p450 enzyme autoinduction. Overexposure seems to be an independent intolerance factor. Although delayed autoinduction is not well established as a reason for adverse events in saquinavir therapy, this observation may be confirmed in the near future by increased use.

Key Words: BOOSTED PROTEASE INHIBITOR • SAQUINAVIR • THERAPEUTIC DRUG MONITORING • DOSE ADJUSTMENT • AUTOINDUCTION

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