INFLUENCE OF A FAT-RICH MEAL ON THE PHARMACOKINETICS OF A NEW ORAL FORMULATION OF CYCLOSPORINE IN A CROSSOVER COMPARISON WITH THE MARKET FORMULATIONS

被引:142
作者
MUELLER, EA
KOVARIK, JM
VANBREE, JB
GREVEL, J
LUCKER, PW
KUTZ, K
机构
[1] SANDOZ LTD,DEPT HUMAN PHARMACOL,DRUG SAFETY ASSESSMENT,CH-4002 BASEL,SWITZERLAND
[2] BIOMED & AGR SERV TEXAS INC,AUSTIN,TX
[3] INST CLIN PHARMACOL,GRUNSTADT,GERMANY
[4] SANDOZ LTD,DEPT BIOPHARMACEUT,CH-4002 BASEL,SWITZERLAND
关键词
CYCLOSPORINE; FOOD EFFECT; PHARMACOKINETICS; FORMULATION;
D O I
10.1023/A:1018922517162
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The influence of a fat-rich meal on the pharmacokinetics of cyclosporine from a new oral formulation (Sandimmune Neoral) was compared in a randomized, four-way crossover study to the currently marketed formulation (Sandimmune) in 24 healthy male volunteers. Single oral doses of 300 mg Sandimmune and 180 mg Sandimmune Neoral were each administered once under fasting conditions and once 30 min after starting a high-fat meal. Serial blood samples were obtained over a 48-hr period after each administration, and whole-blood cyclosporine concentrations were determined by a specific monoclonal radioimmunoassay method. Food had a marked effect on cyclosporine absorption from Sandimmune manifested by a nearly doubled time to reach the peak concentration and a 37% increase in the area under the curve. This was associated with significant elevations in subsequent whole-blood cyclosporine concentrations compared to the fasting administration. For Sandimmune Neoral the influence was less pronounced. The maximum concentration was decreased by 26%, without a relevant change in the time to reach the peak; the area under the curve showed a slight reduction of 15%. The relatively minor influence of a fat-rich meal on the absorption of cyclosporine from Sandimmune Neoral is advantageous when individualizing a dosage regimen under clinical and out-patient administration conditions.
引用
收藏
页码:151 / 155
页数:5
相关论文
共 17 条
  • [1] LONG-TERM CYCLOSPORINE PHARMACOKINETIC CHANGES IN RENAL-TRANSPLANT RECIPIENTS - EFFECTS OF BINDING AND METABOLISM
    AWNI, WM
    KASISKE, BL
    HEIMDUTHOY, K
    RAO, KV
    [J]. CLINICAL PHARMACOLOGY & THERAPEUTICS, 1989, 45 (01) : 41 - 48
  • [2] BALL PE, 1988, CLIN CHEM, V34, P257
  • [3] PHARMACOKINETICS OF ORAL CYCLOSPORINE-A (SANDIMMUN) IN HEALTHY-SUBJECTS
    GREVEL, J
    NUESCH, E
    ABISCH, E
    KUTZ, K
    [J]. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1986, 31 (02) : 211 - 216
  • [4] EFFECT OF FOOD ON THE PHARMACOKINETICS OF CYCLOSPORINE IN HEALTHY-SUBJECTS FOLLOWING ORAL AND INTRAVENOUS ADMINISTRATION
    GUPTA, SK
    MANFRO, RC
    TOMLANOVICH, SJ
    GAMBERTOGLIO, JG
    GAROVOY, MR
    BENET, LZ
    [J]. JOURNAL OF CLINICAL PHARMACOLOGY, 1990, 30 (07) : 643 - 653
  • [5] HIGH-FAT MEALS INCREASE THE CLEARANCE OF CYCLOSPORINE
    GUPTA, SK
    BENET, LZ
    [J]. PHARMACEUTICAL RESEARCH, 1990, 7 (01) : 46 - 48
  • [6] HAUSCHKE D, 1990, INT J CLIN PHARM TH, V28, P72
  • [7] HONCHARIK N, 1991, TRANSPLANTATION, V52, P1087
  • [8] KEOWN PA, 1983, TRANSPLANT P, V15, P2438
  • [9] THE EFFECT OF FOOD AND BILE-ACID ADMINISTRATION ON THE RELATIVE BIOAVAILABILITY OF CYCLOSPORINE
    LINDHOLM, A
    HENRICSSON, S
    DAHLQVIST, R
    [J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1990, 29 (05) : 541 - 548
  • [10] CLINICAL PHARMACOKINETICS OF CYCLOSPORINE
    PTACHCINSKI, RJ
    VENKATARAMANAN, R
    BURCKART, GJ
    [J]. CLINICAL PHARMACOKINETICS, 1986, 11 (02) : 107 - 132