The Cooperstown cocktail refers to a panel of four drug probes used in human
pharmacokinetic
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...
studies to determine the activity of
drug metabolising enzymes. The terminology 'cocktail' refers to the fact that the drug probes are given together.
The Cooperstown cocktail consists of four drugs that are considered specific substrates for four
cytochrome P450
Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
(CYP) isoforms. One of the drugs (
caffeine) provides, through its
metabolites, substrates for two additional enzymes.
Uses
The drugs and the enzymes they probe are as follows - caffeine (probes
CYP1A2,
N-acetyltransferase 2
N-acetyltransferase 2 (arylamine N-acetyltransferase), also known as NAT2, is an enzyme which in humans is encoded by the ''NAT2'' gene.
Function
This gene encodes a type of N-acetyltransferase. The NAT2 isozyme functions to both activate and ...
,
xanthine oxidase),
midazolam (probes
CYP3A),
omeprazole (probes
CYP2C19) and
dextromethorphan (probes
CYP2D6). After giving the cocktail, the concentrations of the drugs and their metabolites in plasma (for midazolam and omeprazole) and urine (for caffeine and dextromethorphan) are determined at various times. By analysing these concentrations, it is possible to determine the activity (i.e. the
phenotype) of the relevant enzyme. Caffeine can be used as a probe for three different enzymes by measuring several of its urinary metabolites and comparing their relative concentrations.
The 'Cooperstown 5 + 1 cocktail', in addition to the four drug probes mentioned above, incorporates
warfarin as well. Warfarin (actually the S-warfarin
enantiomer
In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...
) is a specific probe for CYP2C9. The '+ 1' refers to the vitamin K that is given together with the warfarin to prevent any anticoagulant effect.
The Cooperstown cocktail and the Cooperstown 5 + 1 cocktail are powerful tools for investigating the activity of important drug metabolising enzymes. They are used in human
drug interaction studies in which the ability of a study drug to inhibit or induce cytochrome p450 enzymes is studied.
References
{{Reflist
Combination drugs
Pharmacokinetics