Drug Bioavailability and Therapeutic Effects 1. efficacy2. safety3. applicability4. uniformity (1) E = k 1 f (A, C, S) E A C S k 1 A E = k 2 f (C, S) k 2 ( ) bioavailability 191
rate extent (2-3) 40-50 physiological availability systematic availability bio-phase availability biological availability bioavailability 1977 FDA Bioavailability means the rate and extent to which the active ingredient 192
or therapeutic moiety is absorbed from a drug product and becomes available at the site of drug action. (4) Pharmaceutical availability Biological availability Pharmacological availability - (pharmaceutical availability) (drug design) (dose form design) biological availability (absorption) 193
(distribution) (metabolism) (excretion) (pharmacokinetics) ADME (pharmacodynamics) (2) 1. 1945 Oser (availability) (physiological availability) (%) = 100% ( ) ( first pass effect) (2) 2. (absolute bioavailability) (%) = 100% 194
relative bioavailability (%) = 100% (comparative bioavailability) Comparative bioavailability (%) = comparative bioavailabil i= 100% 100% (bioequivalence) 3. 50% (ED ) ED 50 ED 50 (%) = 100% ED 50 ( ) Extent of bioavailability EB = Rate of bioavailability RB = 195
4. (a) (b) (c) (d) (e) (a)-(c) - ( ) (2-3) - (a) AUC (b) C max (c) T max C max C max T max (MEC) MEC (MTC) - AUCC max T max A BC - B (2-3, 5-6) 1. 2. 3. 4. 1. (a) I (phase I) 20~80 196
g/ml 6.0 4.0 2.0 C max peak T max AUC MEC 0 0.5 1 2 3 4 6 8 10 12 hr A max A B max B C max MTC MEC C TA max TB max TC max - II (phase II) 100~200 III (phase III) 197
IV ( ) (b) (c) ph 1.0 (d) 90% (7-8) 2. (a) (b) (c) ( ) 198
3. griseofulvin ( ) 4. ( ) (5-6) ( ) 1960-1970 1968 diphenylhydantoin ( ) diphenylhydantoin 51 chloramphenicol ( )digoxin ( ) 199
chemical equivalence (genetics) BA/BE (7-8) ( ) 1. (a) (b) (c) (d) (e) (f ) (g) 2. (a) (b) (c) (d) (e) 3. (a) (b) (c) 200
201 4. (a) (b) (c) 5. (a) (b) --------------------- --------------------- --------------------- ------------------------------------------------ ------------------------------------------------ --------------------- --------------------- --------------------- ------------------------------------------------ ------------------------------------------------
(c) 6. (a) (b) (c) 7. (total drug quantity) (patient-oriented) 1. Sezaki, H. (1989). Advances in Biopharmaceutics and Drug Delivery. Jap. J. Clin. Med., 6, 1213-1217. 2. Wagner, J. G. and Pernarowski, M. (1971). Biopharmaceutics and Relevant Pharmacokinetics. Drug Intelligence Pub. Hamilton, IL, U.S.A. 3. Prescott, L. F. and Nimmo, W. S. (1979). Drug Absorption, ADIS Press, New York, U. S. A. 4. Chien, Y. W. (1982). Novel Drug Delivery Systems. pp. 1-11, Marcel Dekker, Inc., New York, U.S.A. 5. Abdou, H. M. (1989). Dissolution, Bioavailability and Bioequivalence. Mack Pub. Co., Easton, PA, U.S.A 6. (1989).,. 202
7. Ansel, H. C., Popovich, N. G., and Allen, L. V. (1995). Pharmaceutical Dosage Forms and Drug Delivery Systems. 6 th Ed., pp. 55-98, Williams & Wilkins, Baltimore, U.S.A. 8. Florence, A. T. and Attwood, D. (1998). Physicochemical Principles of Pharmacy. 3 rd Ed., pp. 372-448, Macmillan Press Ltd., London, England. 203
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