Trust, but Verify: Translating Dosing Evidence to Understudied Populations in Low- and Middle-Income Countries.

Drug dosing recommendations derived from healthy volunteers and selected preregistration populations may not translate reliably to physiologically distinct or understudied groups, particularly in low- and middle-income countries. Using a metformin-dolutegravir drug interaction study and colistin pharmacokinetic study from South Africa, we illustrate how body composition and disease severity, respectively, can alter dosing assumptions. Drug development and post-registration programs should include explicit translation plans using target-population data to confirm, refine, or revise dosing recommendations in understudied target populations.