Impact of population pharmacokinetic-pharmacodynamic analyses on the drug development process - Experience at Parke-Davis

被引:21
作者
Olson, SC [1 ]
Bockbrader, H [1 ]
Boyd, RA [1 ]
Cook, J [1 ]
Koup, JR [1 ]
Lalonde, RL [1 ]
Siedlik, PH [1 ]
Powell, JR [1 ]
机构
[1] Warner Lambert Parke Davis, Parke Davis Pharmaceut Res Div, Ann Arbor, MI 48105 USA
关键词
D O I
10.2165/00003088-200038050-00005
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: Continued scepticism about the benefits of population pharmacokinetics and/or population pharmacodynamics, here referred to collectively as the population approach, hampers its widespread application in drug development. At the same time the sources of this scepticism have not been clearly defined. In an attempt to capture and clearly define these concerns and to help communicate the value of the population approach in drug development at Parke-Davis we conducted a survey of customers within the company. The results of this survey are presented here. Methods: All drug development programmes conducted over the past 10 years that included a population approach in data analysis and interpretation were identified. A brief description of the population analysis was prepared together with a brief description of how the resulting information was used in each drug development programme. These synopses were forwarded to relevant members of each drug development team together with a survey designed to solicit opinions as to the relevance and impact of these analyses. Results: The most frequent use of information derived from population-based analysis was in labelling. In all cases of drugs making to New Drug Application (NDA) submission the analyses resulted in information that was included in approved or proposed labelling. In almost half of the cases summarised here (5 of 12), population-based analysis was perceived to have resulted in information that influenced the direction of individual development programmes. In many of these cases the information was serendipitous. It is also noted that most of these analyses were not the result of clearly defined objectives and prospective analysis plans. Conclusions: Use of the population approach, even when applied retrospectively, may have value in complementing or supporting interpretation of other data collected during the course of a trial. Atypical systemic exposure is quickly and easily assessed for correlation with adverse events or exceptional efficacy in retrospective or ad hoc evaluation. Although we know of no direct evidence, it is possible that such use of population pharmacokinetic data has facilitated NDA review and approval by providing insight into the role of atypical systemic drug exposure in otherwise spurious events.
引用
收藏
页码:449 / 459
页数:11
相关论文
共 17 条
  • [1] A CONTRACEPTIVE VAGINAL RING RELEASING NORETHINDRONE ACETATE AND ETHINYL ESTRADIOL
    BALLAGH, SA
    MISHELL, DR
    LACARRA, M
    SHOUPE, D
    JACKANICZ, TM
    EGGENA, P
    [J]. CONTRACEPTION, 1994, 50 (06) : 517 - 533
  • [2] DOSE-FINDING STUDY OF A CONTRACEPTIVE RING RELEASING NORETHINDRONE ACETATE ETHINYL ESTRADIOL
    BALLAGH, SA
    MISHELL, DR
    JACKANICZ, TM
    LACARRA, M
    EGGENA, P
    [J]. CONTRACEPTION, 1994, 50 (06) : 535 - 549
  • [3] Beal S.L., 1992, NONMEM USERS GUIDE 1
  • [4] Boucher BA, 1996, PHARMACOTHERAPY, V16, P638
  • [5] Eldon MA, 1998, NEUROLOGIST, V4, pS23
  • [6] ETTE EI, 1997, POPULATION APPROACH, P271
  • [7] FLACK MR, 1996, 52 ANN M AM SOC REPR, pS56
  • [8] CLINICAL PHARMACOKINETICS OF ANTIEPILEPTIC DRUGS IN ADULTS
    MORSELLI, PL
    FRANCOMORSELLI, R
    [J]. PHARMACOLOGY & THERAPEUTICS, 1980, 10 (01) : 65 - 101
  • [9] *PARK, 1996, PLASM FOSPH
  • [10] An evaluation of the integration of pharmacokinetic and pharmacodynamic principles in clinical drug development - Experience within Hoffmann La Roche
    Reigner, BG
    Williams, PEO
    Patel, JH
    Steimer, JL
    Peck, C
    vanBrummelen, P
    [J]. CLINICAL PHARMACOKINETICS, 1997, 33 (02) : 142 - 152