title: Dose reduction effective in alleviating symptoms of saquinavir toxicity.
abstract: 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.
authors.affiliation: Medical HIV Treatment and Research Unit, Hospital of the Johann Wolfgang Goethe University, Department of Internal Medicine II, Frankfurt, Germany. c.stephan@em.uni-frankfurt.de
authors.forename: C
authors.initials: C
authors.lastname: Stephan
authors.forename: A
authors.initials: A
authors.lastname: Carlebach
authors.forename: C
authors.initials: C
authors.lastname: Rottmann
authors.forename: A
authors.initials: A
authors.lastname: Haberl
authors.forename: B
authors.initials: B
authors.lastname: Dauer
authors.forename: N
authors.initials: N
authors.lastname: von Hentig
authors.forename: M
authors.initials: M
authors.lastname: Kurowski
authors.forename: S
authors.initials: S
authors.lastname: Staszewski
mesh_terms: D000328:Adult; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D019438:Ritonavir / Q000008:administration & dosage; D019258:Saquinavir / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D017320:HIV Protease Inhibitors; D019258:Saquinavir; D019438:Ritonavir