Increased systemic availability of loperamide after oral administration of loperamide and loperamide oxide with cotrimoxazole

Abstract

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,,,, C,,, and AUC of loperamide oxide, whereas the C,,, (0.32 k0.14 ng ml-' without cotrimoxazole; 0.45 k 0.18 ng ml-' with cotrimoxazole; P < 0.05) and AUC (8.13 & 1.91 ng ml-' h without cotrimoxazole; 12.50f4.60 ng ml-' h with cotrimoxazole; P < 0.005) of loperamide were significantly increased. 3 Coadministration of cotrimoxazole with loperamide significantly increased the C, , , (0.74k0.22 ng ml-' without cotrimoxazole; 1.49k0.81 ng ml-' with cotrimoxazole; P < 0.01) and AUC ( 13.40 f 3.80 ng ml-I h without cotrimoxazole; 25.30+ 11.10 ng ml-I h with cotrimoxazole; P<0.005) of loperamide, whilst its t,,, and t1,2,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.

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