Tipranavir Loperamide

Ritonavir increases the piasma levels of loperamide. Tipranavir, aione and combined with ritonavir, reduces the bioavailability and piasma ieveis of ioperamide and its metabolites. No central opioid adverse effects are seen when loperamide is given with ritonavir aione, tipranavir aione, or tipranavir/ritonavir. 

Drugs that may affect tipranavir include aluminum- and magnesium-based antacids, azole antifungals, clarithromycin, efavirenz, loperamide, NRTIs (ie, didanosine, zidovudine), rifamycins (rifampin), St. John s wort, tenofovir. 

Mukwaya, G., MacGregor, T., Hoelscher, D., Heming, T., Legg, D., Kavanaugh, K., Johnson, P., Sabo, J. P., and McCallister, S. (2005) Interaction of ritonavir-boosted tipranavir with loperamide does not result in loperamide-associated neurologic side effects in healthy volunteers. Antimicrob. Agents Chemother. 49, 4903-4910. 

In a double-blind, placebo-controlled study, 12 healthy subjects were given a single 600-mg dose of ritonavir with either loperamide 16 mg or placebo. The loperamide AUC and maximum plasma level were increased threefold and 17%, respectively, by ritonavir, but no additional CNS adverse effects were seen. Anotiier study in 20 healthy subjects looked at the pharmacokinetics and pharmacodynamics of a single 16-mg dose of loperamide taken with either tipranavir 750 mg twice daily, ritonavir 200 mg twice daily or both drugs together. (Note that this dose of tipranavir is higher than tiie usual ritonavir-boosted dose of 500 mg twice daily.) Tipranavir alone reduced the maximum concentration and AUC of loperamide by 58% and 63%, respectively, whereas ritonavir increased these parameters by 83% and 121%, respectively. The combination of tipranavir/ritonavir, as is usual clinical practice, resulted in a net reduction in the maximum concentration and AUC of loperamide by 61% and 51%, respectively, similar to the effect seen with tipranavir alone. The maximum concentration and AUC of the metabolites of loperamide were also reduced. There were no clinically significant loperamide adverse effects on respiration or pupil contractility with either ritonavir alone, tipranavir alone, or the combination. ... 

The clinical relevance of the decrease in loperamide bioavailability with tipranavir alone or tipranavir/ritonavir is unknown. 

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