Publication:

Propantheline induced pharmacokinetic variability in lithium bioavailability in human volunteers after co-administration with lithium and imipramine

Background Lithium is used commonly in bipolar illness. It is co administered with many other drugs like imipramine, fluoxetine to improve the clinical efficacy of the therapy. Co administrations of other drugs like NSAIDS and GIT drugs for various ailments are also common. As this drug possesses a narrow therapeutic range, effect of other drugs on its pharmacokinetic parameters is important to achieve its therapeutic goal as well as to avoid serious adverse effect.

Methods Total n= 30 human volunteers were enrolled in the study. After randomization subjects were divided into three study groups. Group 1 was given lithium (900mg) alone while group 2 and 3 were given lithium (900mg) and imipramine (25mg) at 0h. Group 3 patients were administered propantheline (15mg) 1 hr prior to lithium and imipramine.

Results In group 2 (Li+Imp) treatment with imipramine produced a significant decrease in C max (p<0.01), increase in Tmax (p<0.001) and a significant fall in AUC (p<0.001) of lithium. There was no significant change in Kel and hence no change in T1/2 was observed. In group 3 ((Li+Imp+Pro) addition of propantheline accentuated the imipramine induced fall in serum lithium concentration at all the sampling points as shown in Fig 1.It significantly accentuated the imipramine induced fall in Cmax of lithium (p<0.05) and prolonged the T max. There was no significant difference between Kel, T 1/2 and AUC of group 2 (Li+Imp) versus group 3 (Li+Imp+Pro).

Conclusions Propantheline even being the anticholinergic drug was unable to show its effect, this is due to high ceiling masking in antagonistic action of imipramine.