Increased Systemic Availability Of Loperamide After Oral Administration Of Loperamide And Loperamide Oxide With Cotrimoxazole

1 The effects of concurrent administration of cotrimoxazole on the plasma concentration-time profiles of loperamide and its oxide were investigated in two separate studies in healthy male volunteers. Cotrimoxazole (960 mg, twice daily) was administered for 24 h before and 48 h after an oral dose of loperamide oxide (4 mg) or loperamide (4 mg).2 Coadministration of cotrimoxazole with loperamide oxide did not alter the t(max), C-max and AUC of loperamide oxide, whereas the C-max (0.32 +/- 0.14 ng ml(-1) without cotrimoxazole; 0.45 +/- 0.18 ng ml(-1) with cotrimoxazole; P < 0.05) and AUC (8.13 +/- 1.91 ng ml(-1) h without cotrimoxazole; 12.50 +/- 4.60 ng ml(-1) h with cotrimoxazole; P < 0.005) of loperamide were significantly increased.3 Coadministration of cotrimoxazole with loperamide significantly increased the C-max (0.74 +/- 0.22 ng ml(-1) without cotrimoxazole; 1.49 +/- 0.81 ng ml(-1) with cotrimoxazole; P < 0.01) and AUC (13.40 +/- 3.80 ng ml(-1) h without cotrimoxazole; 25.30 +/- 11.10 ng ml(-1) h with cotrimoxazole; P < 0.005) of loperamide, whilst its t(max) and t(1/2,z) were not significantly altered.4 The increase in loperamide AUC, following coadministration of either loperamide oxide or loperamide with cotrimoxazole, may be due to reduced first pass metabolism of loperamide.