BDDCS Predictions, Self-Correcting Aspects of BDDCS Assignments, BDDCS Assignment Corrections, and Classification for more than 175 Additional Drugs

Abstract

Abstract. The biopharmaceutics drug disposition classification system was developed in 2005 by Wu and Benet as a tool to predict metabolizing enzyme and drug transporter effects on drug disposition. The system was modified from the biopharmaceutics classification system and classifies drugs according to their extent of metabolism and their water solubility. By 2010, Benet et al. had classified over 900 drugs. In this paper, we incorporate more than 175 drugs into the system and amend the classification of 13 drugs. We discuss current and additional applications of BDDCS, which include predicting drug-drug and endogenous substrate interactions, pharmacogenomic effects, food effects, elimination routes, central nervous system exposure, toxicity, and environmental impacts of drugs. When predictions and classes are not aligned, the system detects an error and is able to self-correct, generally indicating a problem with initial class assignment and/or measurements determining such assignments.

BDDCS, the Rule of 5 and drugability

“…In that paper [1], Wu and Benet cautioned that “there will always be exceptions to the broad, general rules presented here”. Yet even when the BDDCS classification was expanded to more than 900 drugs [17] and most recently an additional 175 drugs were added [18], the predictions in Fig. 1 for the BDDCS Class 1 drugs holds remarkably well and we do not know of any class 1 drugs that require a dosage change as a result of transporter inhibition or induction.…”

“…Varma et al [19] have fallen into the trap noted in Fig. 1; BDDCS Class 1 compounds, which represent 37.5% of classified drugs [17, 18], can be shown to be substrates of transporters, but these transporter effects are clinically insignificant. The disposition of the remaining 62.5% of classified drugs may be modified by transporters.…”

“…In general, now with the BDDCS Classification expanded to more than 1,100 drugs and active metabolites (primarily active compounds from prodrugs) [17,18], the predictions in Fig. 1 and the relationship between intestinal permeability and metabolism hold up quite well, such that we do not know of any drugs predicted to not have a clinically relevant transporter effect (37.5% of drugs) that exhibit a relevant transporter effect in the clinic, thus leading to the potential drug-drug interaction (DDI) predictability of BDDCS.…”

“…More recently, Hosey et al [18] incorporated an additional 175 drugs into the system and amended the classification of 11 drugs from the previous compilation. Our analysis here evaluates the more than 1100 drugs compilation as amended, where we have excluded 14 Class 0 drugs (those drugs where the extent of metabolism and BDDCS class would change dependent upon urine pH), 31 active metabolites (when the active metabolite is not also marketed in a regulatory approved dosage form) and 11 drugs for which we could not confirm an approval history.…”

Use of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to Help Predict the Occurrence of Idiosyncratic Cutaneous Adverse Drug Reactions Associated with Antiepileptic Drug Usage

“…BDDCS provides a useful tool in early drug discovery for predicting routes of elimination, oral drug disposition, food effects on drug absorption, transporter effects on drug absorption, and potentially clinically significant drug interactions that may arise in the intestine, liver, and brain (15,16). BDDCS recognizes that drugs exhibiting a high passive intestinal permeability rate (BDDCS class 1 and BDDCS class 2) are extensively metabolized in humans, while low passive permeability rate drugs (BDDCS class 3 and BDDCS class 4) are primarily eliminated as unchanged drug in the bile or the urine ( Figure S1).…”