Pharmacokinetics multiple dosing and

Koup, J. R., Tucker, E., Thomas, D. J., Kinkel, A. W., Sedman, A. J., Dyer, R., Sharoky, M. A single and multiple dose pharmacokinetic and metabolism study of meclofenamate sodium, Biopharm. Drug Dispos. 1990, 11, 1-15. 

AUen A, Bygate E, Vousden M, Ohver S, Johnson M, Ward C, Cheon A, Choo YS, Kim I. Multiple-dose pharmacokinetics and tolerabihty of gemifloxacin administered orally to healthy volunteers. Antimicrob Agents Chemother 2001 45(2) 540-5. 

Kovarik JM, Mueller EA, Zehender H, Denouel J, Caplain H, Millerioux L. Multiple-dose pharmacokinetics and distribution in tissue of terbinafine and metabohtes. Antimicrob Agents Chemother 1995 39(12) 2738-41. 

Martin DE, Blum R, Doto J, Galbraith H, Ballow C (2007) Multiple-dose pharmacokinetics and safety of bevirimat, a novel inhibitor of HIV maturation, in healthy volunteers. Clin Pharmacokinet 46 589 598... 

McDowell, J.A. Lou, Y. Symonds, W.S. Stein, D.S. Multiple-dose pharmacokinetics and pharmacodynamics of abacavir alone and in combination with zidovudine in human immimodeflciency virus-infected aAwlts, Antimicrob.Agents Chemother., 2000, 44, 2061-2067. 

Zhou, Z. L. et al. (2006). Multiple dose pharmacokinetics of risperidone and 9-hydroxyrisperidone in Chinese female patients with schizophrenia. Acta Pharmacol. Sin., 27, 381-6. 

Exposure Assessment. Single and multiple dose pharmacokinetics, toxicokinetics and tissue distribution studies in relevant species are useful. Proteins are not given orally demonstrating absorption and mass balance is not typically a primary consideration. Rather, this segment of the test should be designed to determine... 

Human pharmacology (Phase I) Assess tolerance Define/describe pharmacokinetics and pharmacodynamics Explore drug metabolism and drug interactions Estimate activity Dose-tolerance studies Single and multiple dose PK and/or PD studies Drug interaction studies... 

Labellarte, M., Zumbrunnen, T., Brennan,/., Biederman, J., Connor, J., Emslie, J., Ferguson, J., Khan, A., Ruckle, J., Sallee, R., and Riddle, M. (in press) Multiple-dose pharmacokinetics of fluvox-amine in children and adolescents. / Am Acad Child Adolesc Psychiatry. 

Modi NB, Lindemulder B, Gupta SK Single- and multiple-dose pharmacokinetics of an oral once-a-day osmotic controlled-release OROS (meth-ylphenidate HCL) formulation. J Clin Pharmacol 40 379-388, 2000a... 

Yasui N, Kondo T, Furukori H, et al. Effects of repeated ingestion of grapefruit juice on the single and multiple oral-dose pharmacokinetics and pharmacodynamics of alprazolam. Psychopharmacology (Berl) 2000 150(2) 185-190. 

Single- and multiple-dose pharmacokinetic studies with extracts of SJW were performed in rats and humans, which focused on the determination of plasma levels of the naphthodianthrones hypericin and pseudohypericin and the phloroglucinol derivative hyperforin. Results from pharmacokinetic... 

Wilson, J.M., Cohen, R.I., Kezer, E.A., Schange, S.J., Smith, E.R. Single- and multiple-dose pharmacokinetics ofdezocine in patients with acute or chronic pain, J. Clin. Pharmacol. 1995, 35, 398-403. 

Schumacher S, Abbasi I, Weise D, Hatorp V, Sattler K, Sieber J, Hasslacher C. Single- and multiple-dose pharmacokinetics of repaglinide in patients with type 2 diabetes and renal impairment. Eur J Clin Pharmacol 2001 57(2) 147-52. 

Modeling to Predict Single- and Multiple-Dose Pharmacokinetic Profiles 98... 

The formation of active metabolites has complicated studies on the pharmacokinetics of the benzodiazepines in humans because the elimination half-life of the parent drug may have little relationship to the time course of pharmacologic effects. Those benzodiazepines for which the parent drug or active metabolites have long half-lives are more likely to cause cumulative effects with multiple doses. Cumulative and residual effects such as excessive drowsiness appear to be less of a problem with such drugs as estazolam, oxazepam, and lorazepam, which have shorter half-lives and are metabolized directly to inactive glucuronides. Some pharmacokinetic properties of selected benzodiazepines are listed in Table 22-1. 

The single and multiple-dose pharmacokinetics of citalopram are linear and dose-proportional in the range 10-60 mg/day. Citalopram is metabolized to demethylcitalo-pram, didemethylcitalopram, citalopram-N-oxide, and a deaminated propionic acid derivative. Citalopram has a mean half-life of about 35 hours (4). Racemic citalopram is several times more potent than its metabolites in inhibiting serotonin reuptake (5). 

Kearns GL, Kemp SF, Frindik JP. Single and multiple dose pharmacokinetics of methionyl growth hormone in children with idiopathic growth hormone deficiency. J Clin Endocrin Metabol 1991 72 1148-56. 

The single- and multiple-dose pharmacokinetics of ebastine (10 mg) have been determined in elderly and young healthy subjects using 24-hour Holter monitoring (37). There were no clinically relevant effects. 

Affrime M, Banfield C, Gupta S, Cohen A, Boutros T, Thonoor M, Cayen M. Effect of race and sex on single and multiple dose pharmacokinetics of desloratadine. Clin Pharmacokinet 2002 41(Suppl l) 21-8. 

Richens A, Banfield CR, Salfi M, Nomeir A, Lin CC, Jensen P, Affrime MB, Glue P. Single and multiple dose pharmacokinetics of felbamate in the elderly. Br J Qin Pharmacol 1997 44(2) 129-34. 

Hassan Alin M, Ashton M, Kihamia CM, Mtey GJ, Bjorkman A. Multiple dose pharmacokinetics of oral artemisinin and comparison of its efficacy with that of oral artesu-nate in falciparum malaria patients. Trans R Soc Trop Med Hyg 1996 90(l) 61-5. 

Lackey, M.N., Belknap, E.B., Greco, D.S. Fettman, M.J. (1996) Single intravenous and multiple dose pharmacokinetics of gentamicin in healthy llamas. American Journal of Veterinary Research, 57, 1193-1199. 

Swan, G.E., Guthrie, A.J., Mulders, M.S.G., Killeen, V.M., Nueton, J.P., Short, C.R. van den Berg, J.S. (1995) Single and multiple dose pharmacokinetics of gentamicin administered intravenously and intramuscularly in adult conditioned Thoroughbred mares. Journal of the South African Veterinary Association, 66, 151-156. 

FIGURE 9.31 Multiple dose pharmacokinetics. (A) Nonlinear pharmacokinetics are operative if the tl/2 for elimination increases with increasing dose. If x is chosen to be t,/2 and g t1/2 remains constant, then a steady state will g be obtained after five half-time periods. How- c ever, if no steady state is achieved (and plasma 8 concentrations keep increasing, as shown in the Q graph), then the elimination is being reduced [Pg.210]

Single-dose pharmacokinetics including relationship between dose and plasma concentration, absorption rate, total, metabolic and renal clearance, volume of distribution, elimination rate constant and half-life Multiple-dose pharmacokinetics... 

El-Tahtawy AA, Jackson AJ, Ludden TM. Comparison of single and multiple dose pharmacokinetics using clinical bioequivalence data and Monte Carlo simulations. Pharm Res 1994 11 1330-1336. 

Describe or define pharmacokinetics (PK) and Single and multiple dose PK and/or PD studies... 

W. Wang and S. Ouyang, The formulation of the principle of superposition in the presence of non-compliance and its application in multiple dose pharmacokinetics. J Pharmacokinet Pharmacodyn 26 457—469 (1998). 

---