Abstract
To facilitate specific product development, AUCs obtained over time intervals of interest, known as partial AUC, can be used for bioavailability and bioequivalence assessment. Partial AUC, which describes shapes of pharmacokinetic profiles, is most useful in products with complicated release mechanisms where traditional bioequivalence variables such as C max and AUC0–∞ are not sufficient to distinguish performance of products and ensure therapeutic equivalence. In this chapter, the utility of partial AUC in formulations with same release mechanism, formulations with multimodal release mechanisms, and formulations with different release mechanisms are discussed in detail.
Opinions expressed in this chapter are those of the authors and may not necessarily reflect the position of the Food and Drug Administration.
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References
Banerjee SK, Jagannath C, Hunter RL, Dasgupta A (2000) Bioavailability of tobramycin after oral delivery in FVB mice using CRL-1605 copolymer, an inhibitor of P-glycoprotein. Life Sci 67(16):2011–2016
Bylund J, Bueters T (2013) Presystemic metabolism of AZ’0908, a novel mPGES-1 inhibitor: an in vitro and in vivo cross-species comparison. J Pharm Sci 102(3):1106–1115
21CFR320.1 Bioavailability and bioequivalence requirements [Online]. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=320.1. Accessed 8 Dec 2013
Chen ML (1992) An alternative approach for assessment of rate of absorption in bioequivalence studies. Pharm Res 9(11):1380–1385
Chen ML, Shah VP, Ganes D, Midha KK, Caro J, Nambiar P, Rocci ML Jr, Thombre AG, Abrahamsson B, Conner D, Davit B, Fackler P, Farrell C, Gupta S, Katz R, Mehta M, Preskorn SH, Sanderink G, Stavchansky S, Temple R, Wang Y, Winkle H, Yu L (2010a) Challenges and opportunities in establishing scientific and regulatory standards for determining therapeutic equivalence of modified-release products: workshop summary report. Clin Ther 32(10):1704–1712
Chen ML, Shah VP, Ganes D, Midha KK, Caro J, Nambiar P, Rocci ML Jr, Thombre AG, Abrahamsson B, Conner D, Davit B, Fackler P, Farrell C, Gupta S, Katz R, Mehta M, Preskorn SH, Sanderink G, Stavchansky S, Temple R, Wang Y, Winkle H, Yu L (2010b) Challenges and opportunities in establishing scientific and regulatory standards for assuring therapeutic equivalence of modified release products: workshop summary report. AAPS J 12(3):371–377
Chen ML, Shah VP, Ganes D, Midha KK, Caro J, Nambiar P, Rocci ML Jr, Thombre AG, Abrahamsson B, Conner D, Davit B, Fackler P, Farrell C, Gupta S, Katz R, Mehta M, Preskorn SH, Sanderink G, Stavchansky S, Temple R, Wang Y, Winkle H, Yu L (2010c) Challenges and opportunities in establishing scientific and regulatory standards for assuring therapeutic equivalence of modified-release products: workshop summary report. Eur J Pharm Sci 40(2):148–153
Chen ML, Davit B, Lionberger R, Wahba Z, Ahn HY, Yu LX (2011) Using partial area for evaluation of bioavailability and bioequivalence. Pharm Res 28(8):1939–1947
Dokoumetzidis A, Macheras P (2000) On the use of partial AUC as an early exposure metric. Eur J Pharm Sci 10(2):91–95
Duquesnoy C, Lacey LF, Keene ON, Bye A (1998) Evaluation of different partial AUCs as indirect measures of rate of drug absorption in comparative pharmacokinetic studies. Eur J Pharm Sci 6(4):259–264
Endrenyi L, Tothfalusi L (2010) Do regulatory bioequivalence requirements adequately reflect the therapeutic equivalence of modified-release drug products? J Pharm Pharmaceut Sci 13(1):107–113
Endrenyi L, Csizmadia F, Tothfalusi L, Chen ML (1998) Metrics comparing simulated early concentration profiles for the determination of bioequivalence. Pharm Res 15(8):1292–1299
FDA (1995) Guidance for industry: immediate release solid oral dosage forms. http://www.fda.gov/downloads/Drugs/Guidances/UCM070636.pdf. Accessed 9 Dec 2013
FDA (1997a) Guidance for industry: SUPAC-MR: modified release solid oral dosage forms. http://www.fda.gov/downloads/Drugs/Guidances/UCM070640.pdf. Accessed 9 Dec 2013
FDA (1997b) Guidance for industry: SUPAC-SS: nonsterile semisolid dosage forms. http://www.fda.gov/downloads/Drugs/Guidances/UCM070930.pdf. Accessed 9 Dec 2013
FDA (1999) Guidance for industry: SUPAC-IR/MR: immediate release and modified release solid oral dosage forms manufacturing equipment addendum. http://www.fda.gov/downloads/Drugs/Guidances/UCM070637.pdf. Accessed 9 Dec 2013
FDA (2003) Guidance for industry: bioavailability and bioequivalence studies for orally administered drug products—general considerations. http://www.fda.gov/downloads/Drugs/…/Guidances/ucm070124.pdf. Accessed 8 Dec 2013
FDA (2010a) Draft guidance on methylphenidate hydrochloride. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM281454.pdf. Accessed 8 Dec 2013
FDA (2010b) Meeting of the advisory committee for pharmaceutical science and clinical pharmacology. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AdvisoryCommitteeforPharmaceuticalScienceandClinicalPharmacology/UCM207955.pdf. Accessed 8 Dec 2013
FDA (2010c) Response to citizen’s petition. Docket No, FDA-2007-P-0182. http://www.regulations.gov/#!documentDetail;D=FDA-2007-P-0182-0017. Accessed 9 Dec 2013
FDA (2011) Draft guidance on zolpidem. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM175029.pdf. Accessed 9 Dec 2013
FDA (2012a) Draft guidance on mesalamine. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM319999.pdf. Accessed 8 Dec 2013
FDA (2012b) U.S. package insert for Topamax®. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020505s050lbl.pdf. Accessed 8 Dec 2013
FDA (2013a) U.S. package insert for Ambien®. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019908s032s034,021774s013s015lbl.pdf. Accessed 9 Dec 2013
FDA (2013b) U.S. package insert for Ambien CR®. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019908s032s034,021774s013s015lbl.pdf. Accessed 9 Dec 2013
FDA (2013c) U.S. package insert for Brintellix®. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204447s000lbl.pdf. Accessed 9 Dec 2013
FDA (2013d) U.S. package insert for Concerta®. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021121s031lbl.pdf. Accessed 8 Dec 2013
FDA (2013e) U.S. package insert for Focalin XR®. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021802s025lbl.pdf. Accessed 8 Dec 2013
FDA (2013f) U.S. package insert for Metadate CD®. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021259s026lbl.pdf. Accessed 8 Dec 2013
FDA (2013g) U.S. package insert for Pentasa®. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020049s025lbl.pdf. Accessed 8 Dec 2013
FDA (2013h) U.S. package insert for Quillivant XR®. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202100s002lbl.pdf. Accessed 8 Dec 2013
FDA (2013i) U.S. package insert for Ritalin®. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/010187s074,018029s044lbl.pdf. Accessed 8 Dec 2013
FDA (2013j) U.S. package insert for Ritalin SR®. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/010187s074,018029s044lbl.pdf. Accessed 8 Dec 2013
FDA (2013k) U.S. package insert for Ritalin LA®. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021284s019lbl.pdf. Accessed 8 Dec 2013
FDA (2013l) U.S. package insert for Trokendi XR®. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/201635s000lbl.pdf. Accessed 8 Dec 2013
Fourie Zirkelbach J, Jackson AJ, Wang Y, Schuirmann DJ (2013) Use of partial AUC (PAUC) to evaluate bioequivalence—a case study with complex absorption: methylphenidate. Pharm Res 30(1):191–202
Gabrielesson J, Weiner D (2001) Pharmacokinetic and pharmacodynamic data analysis: concepts and applications, 3rd edn. Apokekarsocieteten, Stockholm
Gehring R, Martinez M (2012) Assessing product bioequivalence for extended-release formulations and drugs with long half-lives. J Vet Pharmacol 35(Suppl 1):3–9
Haidar SH, Makhlouf F, Schuirmann DJ, Hyslop T, Davit B, Conner D, Yu LX (2008) Evaluation of a scaling approach for the bioequivalence of highly variable drugs. AAPS J 10(3):450–454
Klotz U (2012) The pharmacological profile and clinical use of mesalazine (5-aminosalicylic acid). Arzneimittelforschung 62(2):53–58
Lacey LF, Keene ON, Duquesnoy C, Bye A (1994) Evaluation of different indirect measures of rate of drug absorption in comparative pharmacokinetic studies. J Pharm Sci 83(2):212–215
Lionberger RA, Raw AS, Kim SH, Zhang X, Yu LX (2012) Use of partial AUC to demonstrate bioequivalence of zolpidem tartrate extended release formulations. Pharm Res 29:1110–1120
McEvoy JP, Daniel DG, Carson WH Jr, McQuade RD, Marcus RN (2007) A randomized, double-blind, placebo-controlled, study of the efficacy and safety of aripiprazole 10, 15 or 20 mg/day for the treatment of patients with acute exacerbations of schizophrenia. J Psychiatr Res 41(11):895–905
Pringsheim T, Steeves T (2011) Pharmacological treatment for attention deficit hyperactivity disorder (ADHD) in children with comorbid tic disorders. Cochrane Database Syst Rev. (4): 1–27
Qiu Y, Chen Y, Zhang G (2009) Developing solid oral dosage forms: pharmaceutical theory and practice. Elsevier, Amsterdam
Reppas C, Lacey LF, Keene ON, Macheras P, Bye A (1995) Evaluation of different metrics as indirect measures of rate of drug absorption from extended release dosage forms at steady-state. Pharm Res 12(1):103–107
Rostami-Hodjegan A, Jackson PR, Tucker GT (1994) Sensitivity of indirect metrics for assessing “rate” in bioequivalence studies—moving the “goalposts” or changing the “game”. J Pharm Sci 83(11):1554–1557
Shargel L, Yu A (1999) Applied biopharmaceutics and pharmacokinetics, 4th edn. Appleton & Lange, Stamford, CT
Stier EM, Davit BM, Chandaroy P, Chen ML, Fourie-Zirkelbach J, Jackson A, Kim S, Lionberger R, Mehta M, Uppoor RS, Wang Y, Yu L, Conner DP (2012) Use of partial area under the curve metrics to assess bioequivalence of methylphenidate multiphasic modified release formulations. AAPS J 14(4):925–926
Tozer TN, Bois FY, Hauck WW, Chen ML, Williams RL (1996) Absorption rate vs. exposure: which is more useful for bioequivalence testing? Pharm Res 13(3):453–456
Wang Y (2009) Determining critical PK measures for prediction of therapeutic equivalence of MR products: in silico approaches. AAPS Workshop
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Zhu, H., Uppoor, R.S., Mehta, M., Yu, L.X. (2014). Partial Area Under the Curve: An Additional Pharmacokinetic Metric for Bioavailability and Bioequivalence Assessments. In: Yu, L., Li, B. (eds) FDA Bioequivalence Standards. AAPS Advances in the Pharmaceutical Sciences Series, vol 13. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1252-0_7
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