The present invention is directed to apharmaceutical combination of an opioid and a prostaglandincompound of formula (I):(see formula I)wherein L, M and N are hydrogen, hydroxy, halogen, loweralkyl, hydroxy(lower)alkyl, lower alkanoyloxy or oxo,wherein at least one of L and M is a group other thanhydrogen, and the five-membered ring may have at least onedouble bond； A is -CH3, or -CH2OH, -COCH2OH, -COOH or afunctional derivative thereof； B is single bond, -OH2-CH2-,-CH-CH-, -C.ident.C-, -CH2-CH2-CH2-, -CH-CH-CH2-, -CH2-CH=CH-,-C.ident.C-CH2- or -CH2-C.ident.C-； Z is(see formula II, see formula III, see formula IV)or single bondwherein R4 and R5 are hydrogen, hydroxy, halogen, loweralkyl, lower alkoxy or hydroxy(lower) alkyl, wherein R4 andR5 are not hydroxy and lower alkoxy at the same time； R1 isa saturated or unsaturated bivalent lower or mediumaliphatic hydrocarbon residue, which is unsubstituted orsubstituted with halogen, alkyl, hydroxy, oxo, aryl orheterocyclic group, and at least one of carbon atom in thealiphatic hydrocarbon is optionally substituted by oxygen,nitrogen or sulfur； and Ra is a saturated or unsaturatedlower or medium aliphatic hydrocarbon residue, which isunsubstituted or substituted with halogen, oxo, hydroxy,lower alkyl, lower alkoxy, loweralkanoyloxy,cyclo(lower)alkyl, cyclo(lower)alkyloxy, aryl, aryloxy,heterocyclic group or heterocyclic-oxy group； lower alkoxy；lower alkanoyloxy； cyclo(lower)alkyl； cyclo(lower)alkyloxy；aryl； aryloxy； heterocyclic group； heterocyclic-oxy group,provided that Ra is substituted by halogen or Z is C=O.The combination of the invention is useful for opioid useindications such as pain from various etiologies.
