Drug interactions between tacrolimus and clotrimazole troche: a data mining approach followed by a pharmacokinetic study
| Autor: | Mitsutaka Takada, Atsushi Kawase, Takaya Uno, Sachi Matsuda, Megumi Ikura, Hiromi Takenaka, Akira Oita, Kouichi Hosomi, Satoshi Yokoyama, Nobue Terakawa, Kyoichi Wada |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Graft Rejection Male Antifungal Agents Metabolic Clearance Rate medicine.medical_treatment Biological Availability computer.software_genre 030226 pharmacology & pharmacy Tacrolimus 03 medical and health sciences Adverse Event Reporting System 0302 clinical medicine Pharmacokinetics Risk Factors medicine Data Mining Humans Drug Interactions Pharmacology (medical) 030212 general & internal medicine Clotrimazole Retrospective Studies Pharmacology Heart transplantation United States Food and Drug Administration business.industry General Medicine Middle Aged medicine.disease United States Confidence interval Discontinuation Transplant rejection surgical procedures operative Heart Transplantation Female Data mining Drug Monitoring business computer Immunosuppressive Agents medicine.drug |
| Zdroj: | European Journal of Clinical Pharmacology. 76:117-125 |
| ISSN: | 1432-1041 0031-6970 |
| DOI: | 10.1007/s00228-019-02770-6 |
| Popis: | This study investigated the effects of clotrimazole troche on the risk of transplant rejection and the pharmacokinetics of tacrolimus. The data mining approach was used to investigate whether the use of clotrimazole increased the risk of transplant rejection in patients receiving tacrolimus therapy. Patient data were acquired from the US Food and Drug Administration’s Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the end of 2017. Next, we retrospectively investigated the effect of clotrimazole troche on tacrolimus pharmacokinetics in seven patients who underwent heart transplantation between March and December 2017. The FAERS subset data indicated a significant association between transplant rejection and tacrolimus with clotrimazole [reporting odds ratio 1.92, 95% two-sided confidence interval (95% CI) 1.43–2.58, information component 0.81, 95% CI 0.40–1.23]. The pharmacokinetic study demonstrated a significant correlation between trough concentration (C0) and area under the concentration-time curve of tacrolimus after discontinuation of clotrimazole (R2 = 0.60, P < 0.05) but not before its discontinuation. Furthermore, the median clearance/bioavailability of tacrolimus after discontinuation of clotrimazole was 2.2-fold greater than that before its discontinuation (0.27 vs. 0.59 L/h/kg, P < 0.05). The median C0 decreased from 10.7 ng/mL on the day after discontinuation of clotrimazole to 6.5 ng/mL at 1 day and 5.3 ng/mL at 2 days after its discontinuation. Immediate dose adjustments of tacrolimus may be beneficial to avoid transplant rejection when clotrimazole troche is added or discontinued. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink