Drug interactions with the potential to prevent prodrug activation as a common source of irrational prescribing in hospital inpatients.
OBJECTIVE
Our objective was to investigate the frequency of potential drug-drug interactions between the prodrugs losartan, codeine, and tramadol and drugs known to inhibit their activation in hospitalized patients.


METHODS
The frequency of coadministration between losartan and well-established cytochrome P450 (CYP) 2C9 inhibitors, as well as codeine and tramadol and CYP2D6 inhibitors, was studied by use of data from a university hospital medication database. The study population comprised all patients treated in internal medicine, pulmonary medicine, oncology, and neurology wards (105,533 treatment periods and 65,526 patients) between July 1, 1996, and June 30, 2002 (6 years).


RESULTS
Every fifth patient receiving losartan, codeine, or tramadol was concomitantly taking another drug that has the potential to inhibit the activation of these drugs. During the 6-year time period, 1999 patients were exposed to a potential interaction. Interactions occurred more commonly in internal medicine wards (odds ratio, 2.3; 95% confidence interval, 2.1-2.5) and in women (odds ratio, 1.5; 95% confidence interval, 1.4-1.7).


CONCLUSIONS
Coadministration of drugs that potentially result in inhibition of prodrug activation present a common and unrecognized source of irrational prescribing.
Tirkkonen
Tuire
T
Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland. tuire.trikkonen@utu.fi
Laine
Kari
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000493:pharmacokinetics / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors; D001711:Biotransformation / Q000187:drug effects; D003061:Codeine / Q000493:pharmacokinetics / Q000494:pharmacology; D065729:Cytochrome P-450 CYP2C9; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D030561:Databases, Nucleic Acid; D004347:Drug Interactions; D011307:Drug Prescriptions / Q000191:economics / Q000706:statistics & numerical data*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D019808:Losartan / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008508:Medication Errors; D008510:Medication Systems, Hospital; D008875:Middle Aged; D011355:Prodrugs / Q000378:metabolism*; D012737:Sex Factors; D014147:Tramadol / Q000493:pharmacokinetics / Q000494:pharmacology
D000701:Analgesics, Opioid; D000959:Antihypertensive Agents; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004791:Enzyme Inhibitors; D011355:Prodrugs; D014147:Tramadol; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D019808:Losartan; D003061:Codeine