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Pharmacokinetic interaction between ketoconazole and praziquantel in healthy volunteers.
J Clin Pharm Ther. 2007 Dec; 32(6):585-93.JC

Abstract

BACKGROUND

Praziquantel, a broad-spectrum anthelminthic, has been reported to undergo extensive first-pass metabolism by cytochrome P450 (CYP) enzymes in vivo. Ketoconazole, a potent CYP3A4 inhibitor, is known to markedly increase plasma concentrations of many co-administered drugs. However, no data are available on the potential pharmacokinetic drug interaction between ketoconazole and praziquantel in humans.

OBJECTIVE

To investigate the potential pharmacokinetic interaction of ketoconazole with praziquantel in healthy adult Thai male volunteers.

METHODS

In an open-label, randomized two-phase crossover study, separated by a 2-week period, 10 healthy adult Thai male volunteers ingested a single dose of 20 mg/kg praziquantel alone or with co-administration of 400-mg ketoconazole orally daily for 5 days. Venous blood samples were collected at specific times for a 24-h period. Plasma concentrations of praziquantel were determined using high-performance liquid chromatography. A non-compartmental model was applied for pharmacokinetic parameter analysis of praziquantel.

RESULTS

Concurrent administration of ketoconazole with praziquantel significantly increased the mean area under the curve from time zero to infinity (AUC(0-alpha)) and maximum plasma concentration (Cmax) of praziquantel by 93% (955.94 +/- 307.74 vs. 1843.10 +/- 336.39 ng h/mL; P < 0.01) and 102% (183.38 +/- 43.90 vs. 371.31 +/- 44.63 ng/mL; P < 0.01), respectively, whereas the mean total clearance (Cl/F) of praziquantel was significantly decreased by 58% (2.65 +/- 0.64 vs. 1.11 +/- 0.35 mL/h/kg; P < 0.01).

CONCLUSION

Ketoconazole co-administration alters the pharmacokinetics of praziquantel in humans, possibly through inhibition of CYP3A, particularly CYP3A4, first-pass metabolism of praziquantel. Our data suggest that when praziquantel is co-administered with ketoconazole, the dose of praziquantel could be reduced to half the standard dose of praziquantel to reduce the cost of therapy.

Authors+Show Affiliations

Clinical Pharmacology Laboratory, Department of Pharmacology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, Thailand. wibool.r@psu.ac.thNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18021336

Citation

Ridtitid, W, et al. "Pharmacokinetic Interaction Between Ketoconazole and Praziquantel in Healthy Volunteers." Journal of Clinical Pharmacy and Therapeutics, vol. 32, no. 6, 2007, pp. 585-93.
Ridtitid W, Ratsamemonthon K, Mahatthanatrakul W, et al. Pharmacokinetic interaction between ketoconazole and praziquantel in healthy volunteers. J Clin Pharm Ther. 2007;32(6):585-93.
Ridtitid, W., Ratsamemonthon, K., Mahatthanatrakul, W., & Wongnawa, M. (2007). Pharmacokinetic interaction between ketoconazole and praziquantel in healthy volunteers. Journal of Clinical Pharmacy and Therapeutics, 32(6), 585-93.
Ridtitid W, et al. Pharmacokinetic Interaction Between Ketoconazole and Praziquantel in Healthy Volunteers. J Clin Pharm Ther. 2007;32(6):585-93. PubMed PMID: 18021336.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetic interaction between ketoconazole and praziquantel in healthy volunteers. AU - Ridtitid,W, AU - Ratsamemonthon,K, AU - Mahatthanatrakul,W, AU - Wongnawa,M, PY - 2007/11/21/pubmed PY - 2008/1/30/medline PY - 2007/11/21/entrez SP - 585 EP - 93 JF - Journal of clinical pharmacy and therapeutics JO - J Clin Pharm Ther VL - 32 IS - 6 N2 - BACKGROUND: Praziquantel, a broad-spectrum anthelminthic, has been reported to undergo extensive first-pass metabolism by cytochrome P450 (CYP) enzymes in vivo. Ketoconazole, a potent CYP3A4 inhibitor, is known to markedly increase plasma concentrations of many co-administered drugs. However, no data are available on the potential pharmacokinetic drug interaction between ketoconazole and praziquantel in humans. OBJECTIVE: To investigate the potential pharmacokinetic interaction of ketoconazole with praziquantel in healthy adult Thai male volunteers. METHODS: In an open-label, randomized two-phase crossover study, separated by a 2-week period, 10 healthy adult Thai male volunteers ingested a single dose of 20 mg/kg praziquantel alone or with co-administration of 400-mg ketoconazole orally daily for 5 days. Venous blood samples were collected at specific times for a 24-h period. Plasma concentrations of praziquantel were determined using high-performance liquid chromatography. A non-compartmental model was applied for pharmacokinetic parameter analysis of praziquantel. RESULTS: Concurrent administration of ketoconazole with praziquantel significantly increased the mean area under the curve from time zero to infinity (AUC(0-alpha)) and maximum plasma concentration (Cmax) of praziquantel by 93% (955.94 +/- 307.74 vs. 1843.10 +/- 336.39 ng h/mL; P < 0.01) and 102% (183.38 +/- 43.90 vs. 371.31 +/- 44.63 ng/mL; P < 0.01), respectively, whereas the mean total clearance (Cl/F) of praziquantel was significantly decreased by 58% (2.65 +/- 0.64 vs. 1.11 +/- 0.35 mL/h/kg; P < 0.01). CONCLUSION: Ketoconazole co-administration alters the pharmacokinetics of praziquantel in humans, possibly through inhibition of CYP3A, particularly CYP3A4, first-pass metabolism of praziquantel. Our data suggest that when praziquantel is co-administered with ketoconazole, the dose of praziquantel could be reduced to half the standard dose of praziquantel to reduce the cost of therapy. SN - 0269-4727 UR - https://www.unboundmedicine.com/medline/citation/18021336/Pharmacokinetic_interaction_between_ketoconazole_and_praziquantel_in_healthy_volunteers_ L2 - https://doi.org/10.1111/j.1365-2710.2007.00862.x DB - PRIME DP - Unbound Medicine ER -