RESUMEN
AIMS: To evaluate the effect of severe chronic obstructive pulmonary disease (COPD) on drug metabolism by comparing the pharmacokinetics of patients with severe COPD with healthy volunteers and using the modified Inje drug cocktail. METHODS: This was a single-centre pharmacokinetic study with 12 healthy participants and 7 participants with GOLD D COPD. Midazolam 1 mg, dextromethorphan 30 mg, losartan 25 mg, omeprazole 20 mg, caffeine 130 mg and paracetamol 1000 mg were simultaneously administered and intensive pharmacokinetic sampling was conducted over 8 hours. Drug metabolism by CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP1A2, UGT1A6 and UGT1A9 in participants with COPD were compared with phenotypes in healthy controls. RESULTS: The oral clearance (95% confidence interval) in participants with COPD relative to controls was: midazolam 63% (60-67%); dextromethorphan 72% (40-103%); losartan 53% (52-55%); omeprazole 35% (31-39%); caffeine 52% (50-53%); and paracetamol 73% (72-74%). There was a 5-fold increase in AUC for omeprazole and approximately 2-fold increases for caffeine, losartan, dextromethorphan, and midazolam. The AUC of paracetamol, which is mostly glucuronidated, was increased by about 60%. CONCLUSION: Severe COPD is associated with a clinically significant reduction in oral drug clearance. This may be greater for cytochrome P450 substrates than for glucuronidated drugs. This supports reduced starting doses when prescribing for patients with severe COPD.
Asunto(s)
Preparaciones Farmacéuticas , Enfermedad Pulmonar Obstructiva Crónica , Dextrometorfano , Interacciones Farmacológicas , Humanos , Midazolam , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológicoRESUMEN
Inflammatory bowel disease (IBD) is increasingly common, and results in significant morbidity. Traditional therapies include corticosteroids, aminosalicylates, thiopurines and methotrexate but in more recent years biologics have transformed the management of IBD. However, these agents come with a significant financial cost, making them unavailable for many patients worldwide. Therapeutic drug monitoring (TDM) is an important means to optimise clinical outcomes from pharmacotherapy. Recent studies have also focussed on the cost-effectiveness as an outcome of TDM. TDM of traditional therapies is principally mediated through improved disease control. Cost-savings from TDM of biologic therapies arises mainly from reduced pharmaceutical use with equitable clinical outcomes. This review considers the cost-effectiveness of TDM for IBD therapies, with a focus on recent research into biologic TDM.