Biowaiver monographs for immediate release solid oral dosage forms: efavirenz.

Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence testing for the approval of immediate-release (IR) solid oral dosage forms containing efavirenz as the only active pharmaceutical ingredient (API) are reviewed. Because of lack of conclusive data about efavirenz's permeability and its failure to comply with the "high solubility" criteria according to the Biopharmaceutics Classification System (BCS), the API can be classified as BCS Class II/IV. In line with the solubility characteristics, the innovator product does not meet the dissolution criteria for a "rapidly dissolving product." Furthermore, product variations containing commonly used excipients or in the manufacturing process have been reported to impact the rate and extent of efavirenz absorption. Despite its wide therapeutic index, subtherapeutic levels of efavirenz can lead to treatment failure and also facilitate the emergence of efavirenz-resistant mutants. For all these reasons, a biowaiver for IR solid oral dosage forms containing efavirenz as the sole API is not scientifically justified for reformulated or multisource drug products.

[1]  H. Castro,et al.  In Vitro–In Vivo Correlation of Efavirenz Tablets Using GastroPlus® , 2013, AAPS PharmSciTech.

[2]  Tudor I. Oprea,et al.  BDDCS Applied to Over 900 Drugs , 2011, The AAPS Journal.

[3]  V. Rao,et al.  Impact of superdisintegrants on efavirenz release from tablet formulations , 2010, Acta pharmaceutica.

[4]  S. Khoo,et al.  Intracellular accumulation of efavirenz and nevirapine is independent of P-glycoprotein activity in cultured CD4 T cells and primary human lymphocytes. , 2009, The Journal of antimicrobial chemotherapy.

[5]  L. Milani,et al.  A novel polymorphism in ABCB1 gene, CYP2B6*6 and sex predict single-dose efavirenz population pharmacokinetics in Ugandans. , 2009, British journal of clinical pharmacology.

[6]  F. Maggiolo Efavirenz: a decade of clinical experience in the treatment of HIV , 2009, The Journal of antimicrobial chemotherapy.

[7]  D. Haas,et al.  CYP2B6 variants and plasma efavirenz concentrations during antiretroviral therapy in Port-au-Prince, Haiti. , 2009, The Journal of infectious diseases.

[8]  S. Urien,et al.  Is the Recommended Dose of Efavirenz Optimal in Young West African Human Immunodeficiency Virus-Infected Children? , 2009, Antimicrobial Agents and Chemotherapy.

[9]  M. J. García,et al.  Influence of the Cytochrome P450 2B6 Genotype on Population Pharmacokinetics of Efavirenz in Human Immunodeficiency Virus Patients , 2009, Antimicrobial Agents and Chemotherapy.

[10]  D. Haas,et al.  Associations between CYP2B6 polymorphisms and pharmacokinetics after a single dose of nevirapine or efavirenz in African americans. , 2009, The Journal of infectious diseases.

[11]  B. Best,et al.  Efavirenz – Still First-line King? , 2008, Expert opinion on drug metabolism & toxicology.

[12]  L. Mofenson,et al.  Pharmacokinetics and Pharmacodynamics of Efavirenz and Nelfinavir in HIV‐infected Children Participating in an Area‐under‐the‐curve Controlled Trial , 2008, Clinical pharmacology and therapeutics.

[13]  J. Gao,et al.  Investigation of human pharmacoscintigraphic behavior of two tablets and a capsule formulation of a high dose, poorly water soluble/highly permeable drug (efavirenz). , 2007, Journal of pharmaceutical sciences.

[14]  F. Wit,et al.  Efavirenz: a review , 2007, Expert opinion on pharmacotherapy.

[15]  J. Marier,et al.  Comparative bioavailability of a generic capsule formulation of the reverse transcriptase inhibitor efavirenz and the innovator product. , 2006, International journal of clinical pharmacology and therapeutics.

[16]  S. Khoo,et al.  Intracellular and plasma pharmacokinetics of efavirenz in HIV-infected individuals. , 2005, The Journal of antimicrobial chemotherapy.

[17]  R. Farinotti,et al.  Effect of efavirenz on intestinal p-glycoprotein and hepatic p450 function in rats. , 2005, Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques.

[18]  Jennifer B Dressman,et al.  Classification of orally administered drugs on the World Health Organization Model list of Essential Medicines according to the biopharmaceutics classification system. , 2004, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[19]  G L Amidon,et al.  Biowaiver monographs for immediate release solid oral dosage forms based on biopharmaceutics classification system (BCS) literature data: verapamil hydrochloride, propranolol hydrochloride, and atenolol. , 2004, Journal of pharmaceutical sciences.

[20]  G. Amidon,et al.  Molecular properties of WHO essential drugs and provisional biopharmaceutical classification. , 2004, Molecular pharmaceutics.

[21]  J. Schubert,et al.  No influence of the P-glycoprotein genotype (MDR1 C3435T) on plasma levels of lopinavir and efavirenz during antiretroviral treatment. , 2003, European journal of medical research.

[22]  David A. Flockhart,et al.  The Cytochrome P450 2B6 (CYP2B6) Is the Main Catalyst of Efavirenz Primary and Secondary Metabolism: Implication for HIV/AIDS Therapy and Utility of Efavirenz as a Substrate Marker of CYP2B6 Catalytic Activity , 2003, Journal of Pharmacology and Experimental Therapeutics.

[23]  D. Greenblatt,et al.  Differential Modulation of P-Glycoprotein Expression and Activity by Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors in Cell Culture , 2002, Pharmaceutical Research.

[24]  P. Watkins,et al.  Hepatic but not intestinal CYP3A4 displays dose‐dependent induction by efavirenz in humans , 2002, Clinical pharmacology and therapeutics.

[25]  S. Heinzl [Critical dose drugs]. , 2001, Medizinische Monatsschrift fur Pharmazeuten.

[26]  A. Telenti,et al.  Efavirenz Plasma Levels Can Predict Treatment Failure and Central Nervous System Side Effects in Hiv-1-infected Patients , 2022 .

[27]  B. Aungst,et al.  P-glycoprotein, secretory transport, and other barriers to the oral delivery of anti-HIV drugs. , 1999, Advanced drug delivery reviews.

[28]  Sean C. Sweetman,et al.  Martindale: The Complete Drug Reference , 1999 .

[29]  Shiyin Yee,et al.  In Vitro Permeability Across Caco-2 Cells (Colonic) Can Predict In Vivo (Small Intestinal) Absorption in Man—Fact or Myth , 1997, Pharmaceutical Research.

[30]  P. Anderson,et al.  L-743, 726 (DMP-266): a novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type 1 reverse transcriptase , 1995, Antimicrobial agents and chemotherapy.

[31]  J. Crison,et al.  A Theoretical Basis for a Biopharmaceutic Drug Classification: The Correlation of in Vitro Drug Product Dissolution and in Vivo Bioavailability , 1995, Pharmaceutical Research.

[32]  L. Kux OF HEALTH AND HUMAN SERVICES Food and Drug Administration , 2014 .

[33]  Sean C. Sweetman Comprar Martindale the complete reference 36th Ed, 2 vols + CD-ROM | Sean Sweetman | 9780853698425 | Pharmaceutical Press , 2009 .

[34]  James Curran,et al.  Scaling Up Antiretroviral Therapy in Resource-Limited Settings: Treatment Guidelines for a Public Health Approach , 2005 .

[35]  S. Kopp PROPOSAL TO WAIVE IN VIVO BIOEQUIVALENCE REQUIREMENTS FOR THE WHO MODEL LIST OF ESSENTIAL MEDICINES IMMEDIATE RELEASE, SOLID ORAL DOSAGE FORMS , 2005 .

[36]  AC Moffat,et al.  Clarke's analysis of drugs and poisons , 2003 .

[37]  Patrick F. Smith,et al.  Clinical Pharmacokinetics of Non-Nucleoside Reverse Transcriptase Inhibitors , 2001, Clinical pharmacokinetics.

[38]  J. Lin,et al.  Nonlinear pharmacokinetics of efavirenz (DMP-266), a potent HIV-1 reverse transcriptase inhibitor, in rats and monkeys. , 1999, Drug metabolism and disposition: the biological fate of chemicals.

[39]  M. Maurin,et al.  Determination of the pKa and pH-solubility behavior of an ionizable cyclic carbamate, (S)-6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4- (trifluoromethyl)-2H-3,1-benzoxazin-2-one (DMP 266). , 1996, Pharmaceutical development and technology.