JAC Advance Access originally published online on February 14, 2008
Journal of Antimicrobial Chemotherapy 2008 61(4):933-938; doi:10.1093/jac/dkn041
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Original research |
Stavudine plasma concentrations and lipoatrophy
1 Department of Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands 2 Nijmegen University Center for Infectious Diseases (NUCI), Nijmegen, The Netherlands 3 Department of Clinical Pharmacy, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Received 19 June 2007; returned 8 July 2007; revised 11 January 2008; accepted 12 January 2008
* Correspondence address. Nijmegen University Center for Infectious Diseases (NUCI) 484, Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Tel: +31-24-3618819; Fax: +31-24-3541734; E-mail: h.terhofstede{at}aig.umcn.nl
Objectives: The objective of this study was to determine the correlation between plasma stavudine concentrations and lipoatrophy (LA), one of the major adverse events in patients on stavudine and one of the major reasons to discontinue stavudine.
Methods: Plasma drug concentrations were retrospectively analysed in patients who were on a stavudine-containing regimen for at least 12 months. We defined two groups of patients: 21 patients with LA and 15 patients without LA or other stavudine-related side effects (i.e. neuropathy).
Results: We analysed stavudine concentrations in 212 plasma samples: 87 in the control group and 125 in the LA group, with a mean of four plasma samples per person (at least two a year). Demographics were comparable in LA patients and controls, except the duration of stavudine use, which was longer in the LA group: 55 versus 42 months in the control group. Overall, LA patients had higher drug exposure to stavudine when compared with the controls, and this was seen in the geometric concentration ratios (CRs), which were 0.978 and 0.741, respectively (P = 0.04), and also a higher percentage of CR values >1.0, representing a drug concentration above the normal population curve (46% versus 23%, P = 0.02). In addition, the duration of stavudine therapy was independently associated with LA (P = 0.05). In the multivariate analysis, both duration of stavudine (P = 0.05) and CR > 1.0 (P = 0.02) were independently correlated with LA.
Conclusions: Monitoring of plasma stavudine concentrations can be useful to prevent stavudine-related LA.
Keywords: HIV infection , pharmacokinetics , nucleoside reverse transcriptase inhibitors , stavudine serum levels