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Evaluation of pharmacokinetic interaction between cetirizine and ritonavir, an HIV-1 protease inhibitor, in healthy male volunteers

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Background

Serious adverse effects have been observed with some non-sedative H1-antihistamines (terfenadine and astemizole) when they were associated with drugs known to inhibit their metabolism. However, this is not a class effect, and this interaction should be considered on a case-by-case basis. The aim of this study was to evaluate the potential of pharmacokinetic interaction between cetirizine and ritonavir, the most potent cytochrome P 450 (CYP) inhibitor.

Methods

An open-label, single-center, one-sequence crossover pharmacokinetic study was conducted in three running periods: cetirizine (CTZ) alone, ritonavir (RTV) alone and then CTZ plus RTV. For each period, steady-state pharmacokinetics were obtained. RTV and CTZ plasma concentrations were determined using validated liquid chromatography methods. The statistical method was based on a 90% confidence interval (CI) for the ratio of population geometric means (combination/drug alone) for each drug and for each parameter [area under the plasma concentration versus time curve (AUC0-τ,ss), value of maximum plasma concentration (Cmax,ss)] and compared to bioequivalence ranges 80–125% and 70–143% for AUC0-τ,ss and Cmax,ss, respectively.

Results

Among the 17 male subjects enrolled (26.4±8.6 years), 16 completed the study (1 withdrawal after the first period). The RTV pharmacokinetic parameter values were not affected by CTZ co-treatment. With RTV, a 42% increase in the CTZ AUC0-τ,ss (3406 versus 4840 μgh/l, 90% CI of 128–158%), a 53% increase in the CTZ elimination half-life (7.8 h versus 11.9 h, P = 0.001), a slight increase (15%) in the CTZ apparent volume of distribution (Vd,ss/ f) (34.7 l versus 39.8 l, P = 0.035), a 29% decrease in the CTZ apparent total body clearance (49.9 ml/min versus 35.3 ml/min, P<0.001) and bioequivalent Cmax,ss (374 μg/l versus 408 μg/l) were observed. No serious drug related adverse effects were notified.

Conclusions

CTZ does not significantly affect the pharmacokinetic parameters of RTV, and the association does not, thus, require a modification of the dosage of the protease inhibitor. The increased extent of exposure to CTZ in healthy subjects, in the presence of RTV administered at high doses, remained in the same range as previously observed in the elderly or in mildly renally impaired subjects.

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Acknowledgements

The authors thank C. De Vos for her role in instigating this study, E. Baltes for useful discussion and M. Rovei for carefully checking the manuscript.

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Authors and Affiliations

  1. Service de Pharmacie Clinique et des Biomatèriaux, Hôpital Bichat-Cl Bernard, 46 rue Henri Huchard, 75018, Paris, France

    G. Peytavin, C. Gautran, A. C. Cremieux, F. Delatour & R. Farinotti

  2. UCB Pharma Braine-L’alleud, Belgium

    C. Otoul & B. Moulaert

  3. UCB Pharma Nanterre, France

    M. Melac & M. Strolin-Benedetti

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  1. G. Peytavin
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  2. C. Gautran
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  3. C. Otoul
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  4. A. C. Cremieux
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  5. B. Moulaert
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  6. F. Delatour
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  8. M. Strolin-Benedetti
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  9. R. Farinotti
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Peytavin, G., Gautran, C., Otoul, C. et al. Evaluation of pharmacokinetic interaction between cetirizine and ritonavir, an HIV-1 protease inhibitor, in healthy male volunteers. Eur J Clin Pharmacol 61, 267–273 (2005). https://doi.org/10.1007/s00228-005-0917-6

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  • DOI: https://doi.org/10.1007/s00228-005-0917-6

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