Table 2.

Recommended in vivo probe substrates for CYPs.

CYP	Probe Substrates	Comments
1A2	Caffeine	Alternative: theophylline: clinical relevance, but concern about selectivity?
2B6	Bupropion	More validation required.
2C8	unclear	Paclitaxel cannot be given to healthy subjects.
2C9	Tolbutamide	Alternatives: flurbiprofen, diclofenac, phenytoin, warfarin
		(all clinically relevant; safety issue with warfarin?)
2C19	Mephenytoin	Availability?
	Omeprazole	Potential contamination from 3A4 pathway?
2D6	Debrisoquine	Availability?
		Alternatives: dextromethorphan (urine pH-dependent renal excretion; potential contamination from downstream 3A4 pathway?); metoprolol (urine pH-dependent renal excretion); desipramine (clinically relevant)
2E1	Chlorzoxazone
3A4	Midazolam (oral)	Not selective for 3A4 vs 3A5
	Midazolam (oral and i.v.)	Separates liver vs gut contributions; need for stable-isotope labelling for concurrent oral and iv administration; staggered oral and iv dosing may avoid use of labelled drug?
	Midazolam (oral) +Erythromycin (i.v.)	Liver vs gut; erythromycin marks 3A4 referentially to 3A5, but precise mechanistic interpretation is confounded by P-glycoprotein transport, and use of radioactive compound (breath test) may be an issue in some countries.
	Simvastatin or Atorvastatin	Availability of metabolite standards