Lithium is a drug of choice for bipolar disorder but has a narrow therapeutic range. Hence it needs to be combined with other antidepressants for better effect. Imipramine delays attainment of peak serum lithium levels by affecting its pharmacokinetics and delays its absorption in GIT. Mechanism underlying this change was studied using various motility modulating drugs like domperidone and loperamide. The study was conducted on forty normal human volunteers divided into four groups of ten each. Control group received only lithium. Remaining groups received one test drug each along with lithium+imipramine. The blood samples were collected at ½ , 1, 2, 4, 6 and 24 hours after lithium administration. Serum lithium levels were analyzed on Electrolyte analyzer (NOVA) using ion selective electrode and various pharmacokinetic parameters were calculated. Domperidone attenuated the effect of imipramine by further increasing Cmax, AUC and t ½ and decreasing tmax and Kel of lithium significantly. Loperamide produced significant fall in C max, AUC and t ½ , and an increase in Kel. Prokinetic and antimotility drugs affect imipramine induced decrease in lithium bioavailability and result in decreasing therapeutic efficacy of lithium. Domperidone being prokinetic can be combined with therapy whereas Loperamide causes decrease in bioavailability of lithium and can lead to therapeutic failure.
Lithium, Imipramine, Domperidone, Loperamide, Pharmacokinetics