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Véronique Dartois, Drug Forgiveness and Interpatient Pharmacokinetic Variability in Tuberculosis, The Journal of Infectious Diseases, Volume 204, Issue 12, 15 December 2011, Pages 1827–1829, https://doi.org/10.1093/infdis/jir662
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(See the article by Srivastava et al, on pages 1951–9.)
An important—but sometimes difficult to quantify—characteristic of a drug is “forgiveness.” Forgiveness (F) is defined as the difference between the medication’s postdose duration of beneficial action (D) and the prescribed dosing interval (I): F = D – I [1]. In plain words, it directly relates to the number of doses that can be skipped without causing detectable disease relapse. Forgiveness arises by 2 major mechanisms: prolonged inhibitory effect of the drug on its target (pharmacodynamics [PD]) and/or prolonged half-life of the drug at the site of action (pharmacokinetics [PK]).
Drug forgiveness has been characterized in several disease areas in which rebound can be measured noninvasively with a readout that accurately reflects the pharmacological effect of the drug in real time. Examples are β blockers, antihypertension drugs, and anti–human immunodeficiency virus (HIV) agents. The emergence of drug-resistant bacteria is a special form of such rebound. When antimicrobial treatment is too short to achieve complete sterilization, but long enough to eradicate the more drug-sensitive microbes, it leaves the less sensitive ones able to multiply when treatment lapses. This phenomenon has been observed during drug holidays with an HIV protease inhibitor [2], and it is well accepted—although not formally proven—as a major factor in the emergence of multidrug-resistant tuberculosis [3–5].
