During the past 20 years considerable progress has been made in developing the science of bioavailabiity/bioequivalence (BA/BE) testing. This paper focuses on a variety of issues and assumptions that may affect the validity of BA/BE studies. Examples are discussed relating to: the effect of gender and menstrual cycle, individual subject bioequivalence and drug product variability, the importance of special patient populations, and the role of the gastric contents in assessing the BA/BE of orally administered dosage forms.
GibaldiM. In: Biopharmaceutics and Clinical Pharmacokinetics.Philadelphia, PA: Lea and Febiger, Inc.; 1991:252–253.
2.
WilsonK.Sex-related differences in drug disposition in man. Clin Pharmacokin.1984;9(3):189–202.
3.
BackstromTJorpesP.Serum Phenytoin, phenobarbital, carbamazepine, albumin; and plasma estradiol, progesterone concentrations during the menstrual cycle in women with epilepsy. Acta Neurol Scandinav.1979;59:63–71.
4.
ShavitGLermanPKorcznADKivitySBecharMGitterS.Phenytoin pharmacokinetics in catamenial epilepsy. Neurology.1984;34:959–961.
5.
KumarNBehariMAhujaGKJaikhaniBL. Phenytoin levels in catamenial epilepsy. Epilepsia.1988;29:155–158.
6.
BruguerolleBToumiMFarajFVervloetDRazzoukH.Influence of the menstrual cycle on theophylline pharmacokinetics in asthmatics. Eur J Clin Pharmacol.1990;39:59–61.
7.
SutkerPBGoistKCAllainANBuggF.Acute alcohol intoxication: sex comparisons on pharmacokinetic and mood measures. Alcohol Clin Exp Res (US).1987;11(6):507–512.
8.
NiauraRSNathanPEFrankensteinWShapiroAPBrickJ.Gender differences in acute psychomotor, cognitive and pharmacokinetic response to alcohol. Addict Behav (England).1987;12(4):345–456.
9.
NayakVKKshirsagerNADesaiNKSatoskarRS. Influence of menstrual cycle on antipyrine pharmacokinetics in healthy Indian female volunteers. Br J Clin Pharmacol.1988;26(5):604–606.
10.
ConradCDHamiltonJA. Recurrent premenstrual decline in serum lithium concentration: Clinical correlates and treatment implications. J Am Acad Child Psych.1986;6:852–853.
11.
MiaskiewiczSLShivelyCAVesellES. Sex differences in absorption kinetics of sodium salicylate. Clin Pharmacol Ther.1982;31:30–37.
12.
KimmelSGousalvesIYoungsDGidwaniFluctuating level of antidepressants premenstrually. J Psychosom Obstet Gynaecol.1992;13: 277–280.
13.
GengoFMFaganSCKinkelWRMcHughWB. Serum concentrations of propranolol and migraine prophylaxis. Arch Neurol.1984;41: 1306–1307.
14.
OramMWilsonKBurnettD.The influence of oral contraceptives on the metabolism of methaqualone in man. Br J Clin Pharmacol.1982;14: 341–345.
15.
StraughnABWoodGCRaghowGMeyerMC. Bioavailability of seven furosemide tablets in man. Biopharm Drug Dispos.1986;7:113–120.
16.
MidhaKKHubbardJWYeungPKFOrmsbyEMcKayGHawesEMKorchinskiEDGurnseyTRowsonMSchwedeR.Application of replicate design. In: MidhaKKBlumeHH, ed. Bio-International Bioavailability, Bioequivalence and Pharmacokinetics.Stuttgart Germany: Medpharm Scientific Publishers; 1993:53–68.
DreyfussDShaderRIHarmatzJSGreenblattDJ. Kinetics and dynamics of single doses of oxazepam in the elderly: implications of absorption rate. J Clin Psychiatry.1986;47:511–514.
19.
WellingPG. In: BridgesJWChasseaudLF, ed. Progress in Drug Metabolism.Vol. 4. New York: John Wiley; 1980:131.
