Ethnic differences in drug disposition may potentially influence therapeutic response to dabigatran, a reversible direct thrombin inhibitor used for the prevention and/or treatment of various thromboembolic disorders. This analysis of data from 18 clinical studies in healthy volunteers and patients with non-valvular atrial fibrillation (AF) or undergoing knee or hip arthroplasty investigated whether there were any clinically relevant differences in the pharmacokinetics and pharmacodynamics of dabigatran, the active form of dabigatran etexilate, between Japanese and Caucasian subjects. In pooled data from 14 phase I trials, total exposure (i.e. area under the plasma concentration-time curve [AUC]) after administration of dabigatran 150 mg once or twice-daily was on average 20% higher in Japanese than Caucasian subjects (median [10^th to 90^th percentile] 1,110 [644–1,824] vs. 924 [420–1,654] ng·h/ml) although the difference between the groups was not significant. Within-trial comparisons in subjects treated with dabigatran 150 mg twice-daily showed that AUC and maximum plasma concentration differed by less than 10% between the two groups. In patients with AF, trough concentrations after administration of 150 mg twice-daily were similar in Japanese and Caucasian subjects (80.1 [34.5–193.8] vs. 71.0 [34.0–190] ng/ml). Various factors, including body weight and renal clearance, may explain these observed pharmacokinetic differences. The relationship between plasma concentration and coagulation markers was similar and indicative of no difference in the exposure-pharmacodynamic response between these two groups. In conclusion, the results of this analysis show that the pharmacokinetics and pharmacodynamics of dabigatran are similar in Japanese and Caucasian subjects and suggest that there is no need for dose adjustment of dabigatran in Japanese subjects.

Purpose To evaluate the pharmacokinetic and pharmacodynamic effects of concomitant administration of single loading doses of clopidogrel or multiple doses of clopidogrel with multiple doses of dabigatran etexilate. Methods This was an open-label trial in healthy male subjects. In part 1 (pilot, n = 8) and part 3 (n = 12), a single dose of clopidogrel (300 or 600 mg, respectively) was given concomitantly with dabigatran etexilate at steady state; part 2 was a randomized, multiple-dose, crossover study with the test treatment being clopidogrel at steady state [300 mg loading dose on day 1, then 75 mg once daily (qd)] with concomitant dabigatran. Results Bioavailability was moderately increased when a loading dose of clopidogrel (300 mg in part 1 and 600 mg in part 3) was administered concomitantly with dabigatran etexilate 150 mg twice daily (bid). Test/reference ratios for AUC_τ,ss were 135% (90% CI 107–169%) and 132% (90% CI 112–156%), respectively. Steady-state dosing of clopidogrel 75 mg qd and dabigatran etexilate 150 mg bid (part 2) demonstrated minor effects on dabigatran pharmacokinetics (AUC_τ,ss ratio test/reference: 91.9%, 90% CI 78.7–107%) or its pharmacokinetic/pharmacodynamic relationships (activated partial thromboplastin time, ecarin clotting time, thrombin time). Similarly, clopidogrel bioavailability remained unchanged by chronic administration of dabigatran etexilate (part 3: ratio test/reference for AUC₀₋₂₄ was 103%; 90% CI 80.3–131%), as did its pharmacodynamic effects on the inhibition of platelet aggregation. Conclusions When given concomitantly, dabigatran etexilate and clopidogrel at clinically relevant doses did not appear to have significant effects on the pharmacokinetic and pharmacodynamic profiles of either agent.

The cytochrome P450 2D6 (CYP2D6) belongs to a group of CYPs considered of utmost importance in the metabolism of xenobiotics. Despite being of only minor abundance in the liver, it is involved in the clearance of >25% of marketed drugs. Accordingly, CYP2D6 can be very efficiently inhibited by a couple of commonly used drugs such as some antidepressants, although induction by any drug has not been observed thus far. CYP2D6 was also one of the first enzymes for which a highly polymorphic expression could be shown leading to a widespread range of functionality, from a complete lack of a functional enzyme to overexpression due to multiplication of active alleles. A clear relationship between the CYP2D6 genotype and adverse events during treatment with CNS-active drugs such as codeine, antidepressants, or antipsychotics could be demonstrated. More recently, some new aspects emerged about the potential endogenous function of CYP2D6 in terms of behavior and brain disorders.

Older adults remain significantly underrepresented in clinical trials. This is concerning because age‐associated physiological changes can alter drug pharmacokinetics and pharmacodynamics. This paper examines the status of older adult representation in clinical trials, analyzes contributing factors, and discusses initiatives to address gaps. Data were collected from studies completed between 2010 and 2025 using ClinicalTrials.gov to assess age‐related inclusion/exclusion criteria. Further, two surveys of pharmaceutical companies were initially conducted to assess age ranges of randomized patients in pivotal trials, what clinical pharmacology approaches were applied to potentially support dosing in older adult patients, whether exclusion criteria disproportionally excluded older patients, reasons older adult patients were not randomized, and whether older patients more often discontinued trials prematurely. Exclusion criterion based on an age cut‐off was rarely applied. Pharmacokinetic analyses were performed for most trials, but only one age‐related dosing recommendation was reported out of 29 products. In a survey of 41 clinical studies, exclusion criteria showed no bias toward exclusion of patients > 80 years. Reasons for not randomizing older patients were diverse and trial dependent. Subjective reasons for non‐randomization at higher frequencies in older patients were patient wish and doctor advice. Discontinuation rate did not reveal a clear age‐related trend. When comparing trial age composition to disease prevalence by age, a mismatch was evident with fewer than expected older patients enrolled. This research identifies the gap between trial participation and disease prevalence by age groups, offering insights for sponsor companies to enhance older adults' inclusion in clinical research.