Rifampicin buspirone

BUSPIRONE RIFAMPICIN L buspirone levels Induction of CYP3A4-mediated metabolism Watch for poor response to buspirone consider increasing the dose... 

Verapamil, diltiazem, erythromycin, and itraconazole all increase the plasma concentration of buspirone. The plasma concentration is decreased almost 10-fold by rifampicin. Grapefruit juice increases the overall subjective effect of the drug (Mahmood and Saha-jwalla, 1999). 

Lamberg TS, Kivisto KT, Neuvonen PJ. Concentrations and effects of buspirone are considerably reduced by rifampicin. Br J Clin Pharmacol 1998 45(4) 381—385. 

Rifampicin, and presumably other enzyme inducers, reduces concentrations of zolpidem, zopiclone, and buspirone (SEDA-22, 42). Drugs that are solely glucuroni-dated (lorazepam, oxazepam, and temazepam) are not affected. 

The effects of rifampicin on the pharmacokinetics and pharmacodynamics of buspirone were investigated in 10 young healthy volunteers. There was a significant reduction in the effects of buspirone in three of the six psychomotor tests used after rifampicin pretreatment. The interaction between rifampicin and buspirone is probably mostly due to increased CYP3A4 activity. Buspirone will most likely have a greatly reduced anxiolytic effect when it is used together with rifampicin or other potent inducers of CYP3A4, such as phenytoin and carbamazepine... 

Kivisto KT, Lamberg TS, Neuvonen PJ. Interactions of buspirone with itraconazole and rifampicin effects on the pharmacokinetics of the active l-(2-pyrimidinyl)-piperazine metabolite of buspirone. Pharmacol Toxicol 1999 84(2) 94-7. 

Zaleplon, zolpidem and zopiclone are metabolised by several cytochrome CYP450 isoenzymes and it has been suggested that because of this, other drugs which affect a particular isoenzyme such as CYP3A4, may have less effect on their metabolism. However, their pharmacokinetics are affected by potent inducers such as rifampicin and by inhibitors such as the azole antifungals. Buspirone undergoes CYP3A4-mediated metabolism in the liver. 

Rifampicin can cause a marked reduction in the plasma levels and effects of buspirone. 

In a randomised, study, buspirone 30 mg daily was given to 10 healthy subjects, before and after they took rifampicin 600 mg daily for 5 days. It was found that rifampicin reduced the total AUC of buspirone by almost 90% and reduced its peak plasma levels by 87%. The pharmacodynamic effects of buspirone were reduced accordingly (as measured by digit symbol substitution, critical flicker fusion, body sway and visual analogue scales for subjecfive drowsiness). ... 

Not fully established, but it is almost certain that rifampicin induces the cytochrome P450 isoenzyme CYP3A4 in the gut and liver, which metabolises buspirone. Therefore the metabolism and clearance of buspirone are increased. 

Direct information appears to be limited to this study but it is consistent with the way rifampicin interacts with many other drugs. This interaction would appear to be clinically important. If both drugs are used be alert for the need to use an increased buspirone dosage. 

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