Development of a Physiologically Based Model for Oseltamivir and Simulation of Pharmacokinetics in Neonates and Infants
详细信息 查看全文
- 作者：Mr Neil Parrott (1)
Brian Davies (2)
Gerhard Hoffmann (1)
Annette Koerner (1)
Thierry Lave (1)
Eric Prinssen (3)
Elizabeth Theogaraj (4)
Thomas Singer (1) - 刊名：Clinical Pharmacokinetics
- 出版年：2011
- 出版时间：September 2011
- 年：2011
- 卷：50
- 期：9
- 页码：613-623
- 全文大小：218KB
- 参考文献：1. Davies BE. Pharmacokinetics of oseltamivir: an oral antiviral for the treatment and prophylaxis of influenza in diverse populations. J Antimicrob Chemother 2010; 65 Suppl. 2: ii5鈥?0 ss="external" href="http://dx.doi.org/10.1093/jac/dkq015">CrossRef
2. Funk DJ, Siddiqui F, Wiebe K, et al. Practical lessons from the first outbreaks: clinical presentation, obstacles, and management strategies for severe pandemic (pH1N1) 2009 influenza pneumonitis. Crit Care Med 2010; 38(4): e30鈥? ss="external" href="http://dx.doi.org/10.1097/CCM.0b013e3181d10522">CrossRef
3. Rowland M, Balant L, Peck C. Physiologically based pharmacokinetics in drug development and regulatory science: a workshop report (Georgetown University, Washington, DC, May 29鈥?0, 2002). AAPS PharmSci 2004; 6(1): E6 ss="external" href="http://dx.doi.org/10.1208/ps060106">CrossRef
4. Manolis E, Pons G. Proposals for model-based paediatric medicinal development within the current European Union regulatory framework. Br J Clin Pharmacol 2009 Oct; 68(4): 493鈥?01 ss="external" href="http://dx.doi.org/10.1111/j.1365-2125.2009.03484.x">CrossRef
5. Rayner CR, Chanu P, Gieschke R, et al. Population pharmacokinetics of oseltamivir when coadministered with probenecid. J Clin Pharmacol 2008; 48(8): 935鈥?7 ss="external" href="http://dx.doi.org/10.1177/0091270008320317">CrossRef
6. Jones H, Parrott N, Jorga K, et al. A novel strategy for physiologically based predictions of human pharmacokinetics. Clin Pharmacokinet 2006; 45(5): 511鈥?2 ss="external" href="http://dx.doi.org/10.2165/00003088-200645050-00006">CrossRef
7. Yang D, Pearce RE, Wang X, et al. Human carboxylesterases HCE1 and HCE2: ontogenic expression, inter-individual variability and differential hydrolysis of oseltamivir, aspirin, deltamethrin and permethrin. Biochem Pharmacol 2009; 7(7): 238鈥?7 ss="external" href="http://dx.doi.org/10.1016/j.bcp.2008.10.005">CrossRef
8. Shi D, Yang D, Prinssen EP, et al. Surge in expression of carboxylesterase-1 during the post-neonatal stage enables a rapid gain of the capacity to activate the anti-influenza pro-drug oseltamivir. J Infect Dis 2011; 203(7): 937鈥?2 ss="external" href="http://dx.doi.org/10.1093/infdis/jiq145">CrossRef
9. Agoram B, Woltosz WS, Bolger MB. Predicting the impact of physiological and biochemical processes on oral drug bioavailability. Adv Drug Deliv Rev 2001; 50 Suppl. 1: S41鈥?7 ss="external" href="http://dx.doi.org/10.1016/S0169-409X(01)00179-X">CrossRef
10. Dressman JB, Amidon GL, Reppas C, et al. Dissolution testing as a prognostic tool for oral drug absorption: immediate release dosage forms. Pharm Res 1998; 15(1): 11鈥?2 ss="external" href="http://dx.doi.org/10.1023/A:1011984216775">CrossRef
11. de Zwart LL, Rompelberg CJM, Sips AJAM, et al. Anatomical and physiological differences between various species used in studies on the pharmacokinetics and toxicology of xenobiotics: a review of literature [report no. 623860010]. Bilthoven: Rijksinstitute voor Volksgezondheit en Milieu, 1999 [online]. Available from URL: ss="a-plus-plus">http://www.rivm.nl/bibliotheek/rapporten/623860010.pdf [Accessed 2011 Jun 14]
12. Davies B, Morris T. Physiological parameters in laboratory animals and humans. Pharm Res 1993; 10(7): 1093鈥? ss="external" href="http://dx.doi.org/10.1023/A:1018943613122">CrossRef
13. Bod茅 S, Dreyer T, Greisen G. Gastric emptying and small intestinal transit time in preterm infants: a scintigraphic method. J Pediatric Gastroenterol Nutr 2004; 39(4): 378鈥?2 ss="external" href="http://dx.doi.org/10.1097/00005176-200410000-00014">CrossRef
14. National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention (CDC). National Health and Nutrition Examination Survey data. Hyattsville, MD: CDC, 2010
15. Price PS, Conolly RB, Chaisson CF, et al. Modeling interindividual variation in physiological factors used in PBPK models of humans. Crit Rev Toxicol 2003; 33(5): 469鈥?03
16. Haddad S. Characterization of age-related changes in body weight and organ weights from birth to adolescence in humans. J Toxicol Environ Health 2001; 64(6): 453鈥?4 ss="external" href="http://dx.doi.org/10.1080/152873901753215911">CrossRef
17. Brown RP, Delp MD, Lindstedt SL, et al. Physiological parameter values for physiologically based pharmacokinetic models. Toxicol Ind Health 1997; 13(4): 407鈥?4
18. Sweeney RE, Langenberg JP, Maxwell DM. A physiologically based pharmacokinetic (PB/PK) model for multiple exposure routes of soman in multiple species. Arch Toxicol 2006; 80(11): 719鈥?1 ss="external" href="http://dx.doi.org/10.1007/s00204-006-0114-0">CrossRef
19. Parrott N, Lave T. Applications of physiologically based absorption models in drug discovery and development. Mol Pharmaceutics 2008; 5(5): 760鈥?5 ss="external" href="http://dx.doi.org/10.1021/mp8000155">CrossRef
20. Rodgers T, Leahy D, Rowland M. Tissue distribution of basic drugs: accounting for enantiomeric, compound and regional differences amongst b-blocking drugs in rat. J Pharm Sci 2005; 94(6): 1237鈥?8 ss="external" href="http://dx.doi.org/10.1002/jps.20323">CrossRef
21. Rodgers T, Rowland M. Physiologically based pharmacokinetic modelling 2: predicting the tissue distribution of acids, very weak bases, neutrals and zwitterions. J Pharm Sci 2006; 95(6): 1238鈥?7 ss="external" href="http://dx.doi.org/10.1002/jps.20502">CrossRef
22. Rodgers T, Rowland M. Mechanistic approaches to volume of distribution predictions: understanding the processes. Pharmaceutical Research 2007; 24(5): 918鈥?3 ss="external" href="http://dx.doi.org/10.1007/s11095-006-9210-3">CrossRef
23. Kearns GL, Abdel-Rahman SM, Alander SW, et al. Developmental pharmacology: drug disposition, action, and therapy in infants and children. N Engl J Med 2003; 349(12): 1157鈥?7 ss="external" href="http://dx.doi.org/10.1056/NEJMra035092">CrossRef
24. Kawai R, Mathew D, Tanaka C, et al. Physiologically based pharmacokinetics of cyclosporine A: extension to tissue distribution kinetics in rats and scale-up to human. J Pharmacol Exp Ther 1998; 287: 457鈥?8
25. Acosta EP, Jester P, Gal P, et al. Oseltamivir dosing for influenza infection in premature neonates. J Infect Dis 2010; 202(4): 563鈥? ss="external" href="http://dx.doi.org/10.1086/654930">CrossRef
26. Ose A, Ito M, Kusuhara H, et al. Limited brain distribution of [3R,4R,5S]-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate (Ro 64-0802), a pharmacologically active form of oseltamivir, by active efflux across the blood-brain barrier mediated by organic anion transporter 3 (Oat3/Slc22a8) and multidrug resistance-associated protein 4 (Mrp4/Abcc4). Drug Metab Dispos 2009; 37: 315鈥?1 ss="external" href="http://dx.doi.org/10.1124/dmd.108.024018">CrossRef
27. Hill G, Cihlar T, Oo C, et al. The anti-influenza drug oseltamivir exhibits low potential to induce pharmacokinetic drug interactions via renal secretion: correlation of in vivo and in vitro studies. Drug Metab Dispos 2003; 30(1): 13鈥? ss="external" href="http://dx.doi.org/10.1124/dmd.30.1.13">CrossRef
28. Bleasby K, Castle JC, Roberts CJ, et al. Expression profiles of 50 xenobiotic transporter genes in humans and pre-clinical species: a resource for investigations into drug disposition. Xenobiotica 2006; 36: 963鈥?8 ss="external" href="http://dx.doi.org/10.1080/00498250600861751">CrossRef
29. Lin JH. Applications and limitations of interspecies scaling and in vitro extrapolation in pharmacokinetics. Drug Metab Dispos 1998; 26: 1202鈥?2
30. Edginton AN, Fotaki N. Oral drug absorption in pediatric populations. In: Dressman JB, Reppas C, editors. Oral drug absorption. New York: Informa Healthcare, 2010: 108鈥?6
31. Freichel C, Prinssen E, Hoffmann G, et al. Oseltamivir is devoid of specific behavioral and other central nervous system effects in juvenile rats at supratherapeutic oral doses. Int J Virol 2009; 5: 119鈥?0 ss="external" href="http://dx.doi.org/10.3923/ijv.2009.119.130">CrossRef
32. Johnson TN. The problems in scaling adult drug doses to children. Arch Dis Child 2008; 93(3): 207鈥?1 ss="external" href="http://dx.doi.org/10.1136/adc.2006.114835">CrossRef
33. Bjorkman S. Prediction of drug disposition in infants and children by means of physiologically based pharmacokinetic (PBPK) modelling: theophylline and midazolam as model drugs. Br J Clin Pharmacol 2005; 59(6): 691鈥?04 ss="external" href="http://dx.doi.org/10.1111/j.1365-2125.2004.02225.x">CrossRef
34. Edginton AN, Schmitt W, Willmann S. Development and evaluation of a generic physiologically based pharmacokinetic model for children. Clin Pharmacokinet 2006; 45(10): 1013鈥?4 ss="external" href="http://dx.doi.org/10.2165/00003088-200645100-00005">CrossRef
35. Ginsberg G, Hattis D, Russ A, et al. Physiologically based pharmacokinetic (PBPK) modeling of caffeine and theophylline in neonates and adults: implications for assessing children鈥檚 risks from environmental agents. J Toxicol Environ Health 2004; 67(4): 297鈥?29 ss="external" href="http://dx.doi.org/10.1080/15287390490273550">CrossRef
36. Johnson TN, Rostami-Hodjegan A, Tucker GT. Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children. Clin Pharmacokinet 2006; 45: 931鈥?6 ss="external" href="http://dx.doi.org/10.2165/00003088-200645090-00005">CrossRef
37. Gentry PR, Covington TR, Clewell HJ. Evaluation of the potential impact of pharmacokinetic differences on tissue dosimetry in offspring during pregnancy and lactation. Regul Toxicol Pharmacol 2003; 38(1): 1鈥?6 ss="external" href="http://dx.doi.org/10.1016/S0273-2300(03)00047-3">CrossRef
38. Pelekis M, Gephart LA, Lerman SE. Physiological-model-based derivation of the adult and child pharmacokinetic intraspecies uncertainty factors for volatile organic compounds. Regul Toxicol Pharmacol 2001; 33(1): 12鈥?0 ss="external" href="http://dx.doi.org/10.1006/rtph.2000.1436">CrossRef
39. Pons G. Expectations from PK-PD modelling and simulation in the evaluation of medicinal products in children [presentation]. European Medicines Agency Workshop on Modelling in Paediatric Medicines; 2008 Apr 14鈥?5; London [online]. Available from URL: ss="a-plus-plus">http://www.ema.europa.eu/docs/en_GB/document_library/Presentation/2009/11/WC500009643.pdf [Accessed 2011 Jun 14]
40. Hoppu K. Can we get the necessary clinical trials in children and avoid the unnecessary ones? Eur J Clin Pharmacol 2009; 65(8): 747鈥? ss="external" href="http://dx.doi.org/10.1007/s00228-009-0675-y">CrossRef - 作者单位：Mr Neil Parrott (1)
Brian Davies (2)
Gerhard Hoffmann (1)
Annette Koerner (1)
Thierry Lave (1)
Eric Prinssen (3)
Elizabeth Theogaraj (4)
Thomas Singer (1)
1. Bau 70/130, Pharmaceuticals Division, F. Hoffmann-La Roche Ltd., Grenzacherstrasse, Basel, Switzerland
2. Clinical Pharmacology, Pharmaceuticals Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland
3. Discovery Neuroscience, Pharmaceuticals Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland
4. Drug Regulatory, Pharmaceuticals Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland - ISSN：1179-1926
文摘
Background: Physiologically based pharmacokinetic (PBPK) modelling can assist in the development of drug therapies and regimens suitable for challenging patient populations such as very young children. This study describes a strategy employing PBPK models to investigate the intravenous use of the neuraminidase inhibitor oseltamivir in infants and neonates with influenza. Methods: Models of marmoset monkeys and humans were constructed for oseltamivir and its active metabolite oseltamivir carboxylate (OC). These models incorporated physicochemical properties and in vitro metabolism data into mechanistic representations of pharmacokinetic processes. Modelled processes included absorption, whole-body distribution, renal clearance, metabolic conversion of the pro-drug, permeability-limited hepatic disposition of OC and age dependencies for all of these processes. Models were refined after comparison of simulations in monkeys with plasma and liver concentrations measured in adult and newborn marmosets after intravenous and oral dosing. Then simulations with a human model were compared with clinical data taken from intravenous and oral studies in healthy adults and oral studies in infants and neonates. Finally, exposures after intravenous dosing in neonates were predicted. Results: Good simulations in adult marmosets could be obtained after model optimizations for pro-drug conversion, hepatic disposition of OC and renal clearance. After adjustment for age dependencies, including reductions in liver enzyme expression and renal function, the model simulations matched the trend for increased exposures in newborn marmosets compared with those in adults. For adult humans, simulated and observed data after both intravenous and oral dosing showed good agreement and although the data are currently limited, simulations in 1-year-olds and neonates are in reasonable agreement with published results for oral doses. Simulated intravenous infusion plasma profiles in neonates deliver therapeutic concentrations of OC that closely mimic the oral profiles, with 3-fold higher exposures of oseltamivir than those observed with the same oral dose. Conclusions: This work exemplifies the utility of PBPK models in predicting pharmacokinetics in the very young. Simulations showed agreement with a wide range of observational data, indicating that the processes determining the age-dependent pharmacokinetics of oseltamivir are well described.