The influence of the sparteine/debrisoquine genetic polymorphism on the disposition of dexfenfluramine

British Journal of Clinical Pharmacology

Volumn 41, Issue 4, 1996, Pages 311-317

  Gross, A S ^a   Phillips, A C ^a   Rieutord, A ^a   Shenfield, G M ^a  

^a ROYAL NORTH SHORE HOSPITAL   (Australia)

Author keywords

Cytochrome P450; Debrisoquine; Dexfenfluramine; Genetic polymorphism

Indexed keywords

CYTOCHROME P450; DEBRISOQUINE; DEXFENFLURAMINE; DEXNORFENFLURAMINE; DRUG METABOLITE; SPARTEINE;

ADULT; AREA UNDER THE CURVE; ARTICLE; BIOTRANSFORMATION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISPOSITION; DRUG METABOLISM; DRUG STRUCTURE; DRUG URINE LEVEL; FEMALE; GENETIC POLYMORPHISM; HUMAN; HUMAN EXPERIMENT; KIDNEY CLEARANCE; MALE; NORMAL HUMAN; ORAL DRUG ADMINISTRATION; PHENOTYPE; PRIORITY JOURNAL;

EID: 0029868823     PISSN: 03065251     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1365-2125.1996.03178.x     Document Type: Article

References (26)

1. McTavish D, Heel RC. Dexfenfluramine. A review of its pharmacological properties and therapeutic potential in obesity. Drugs 1992 43: 713-733.
2. Stewart GO, Stein GR, Davis ME, Findlater P. Dexfenfluramine in Type II diabetes: effect on weight and diabetes control. Med J Aust 1993; 158: 167-169.
3. Campbell DB, Richards RP, Caccia S, Garattini S. Stereoselective metabolism and the fate of fenfluramine in animals and man. In Development of drugs and modern medicines. eds Gorrod JW, Gibson GG, Mitchard M. Chichester: Ellis Horwood, 1986: 298-311.
4. Richards RP, Taylor D, Garattini S, Campbell DB. Stereoselective kinetics and dynamics of fenfluramine enantiomers. Eur J Clin Pharmacol 1989; 36 Suppl: 181 (abstract).
5. Eichelbaum M, Gross AS. The genetic polymorphism of debrisoquine/sparteine metabolism - clinical aspects. Pharmacol Ther 1990; 46: 377-393.
6. Kitchen I, Tremblay J, Andre J, et al. Interindividual and interspecies variation in the metabolism of the hallucigen 4-methoxyamphetamine. Xenobiotica 1979; 9: 397-404.
7. Tucker GT, Lennard MS, Ellis SW, et al. The demethylenation of methylenedioxymethamphetamine ('ecstacy') by debrisoquine hydroxylase (CYP2D6). Biochem Pharmacol 1994; 29: 1151-1156.
8. Grace JM, Kinter MT, Macdonald TL. Atypical metabolism of deprenyl and its enantiomer, (S)-(+)-N,α-dimethyl-N-propynylphenethylamine, by cytochrome P450 2D6. Chem Res Toxicol 1994; 7: 286-290.
9. Otton SV, Wu D, Joffe R, Cheung SW, Sellers EM. Inhibition by fluoxetine of cytochrome P450 2D6 activity. Clin Pharmacol Ther 1993; 53: 401-409.
10. Peart G, Boutagy J, Shenfield GS. Debrisoquine oxidation in an Australian population. Br J Clin Pharmacol 1986; 21: 456-471.
11. Gross AS, Phillips AC, Boutagy J, Shenfield GM. Determination of dexfenfluramine and nordexfenfluramine in urine by high performance liquid chromatography using ultraviolet detection. J Chromatogr 1993; 621: 115-120.
12. Richards RP, Gordon BH, Ings RMJ, Campbell DB, King LJ. The measurement of d-fenfluramine and its metabolite, d-norfenfluramine in plasma and urine with an application to pharmacokinetic studies. Xenobiotica 1989; 19: 547-553.
13. Rowland M, Tozer T. Clinical pharmacokinetics. Second Edition. Philadelphia: Lea and Febiger, 1989.
14. Holford N. MKMODEL Version 5. Cambridge: BIOSOFT, 1994.
15. Cheymol G, Weissenburger J, Poirer JM, Gellee C. Comparative pharmacokinetics of dexfenfluramine in obese and non-obese subjects. Br J Clin Pharmacol 1995; 39: 684-687.
16. Siegel S. Nonparametric statistics for the behavioural sciences. Tokyo: McGraw-Hill Kogakusha Ltd, 1956.
17. Brownsill R, Wallace D, Taylor A, Campbell B. Study of human urinary metabolism of fenfluramine using gas chromatography-mass spectroscopy. J Chromatogr 1991; 562: 267-277.
18. Koymans L, Vermeulen NPE, Van Acker SABE, Te Koppele JM, Heykants JJP, La Vrijsen K, Meuldermans W, Den Kelder GMDO. A predictive model for substrates of cytochrome P450-debrisoquine (2D6). Chem Res Toxicol 1992; 5: 211-219.
19. Smith DA, Jones BC. Speculations on the substrate structure-activity relationship (SSAR) of cytochrome P450 enzymes. Biochem Pharmacol 1992; 44: 2089-2098.
20. Strobl GR, von Kruedener S, Stockigt J, Guengerich FP, Wolff T. Development of a pharmacophore of inhibition of human liver cytochrome P-450 2D6: Molecular modeling and inhibition studies. J Med Chem 1993; 36: 1136-1145.
21. Kroemer HK, Eichelbaum M. 'It's the genes, stupid' Molecular basis and clinical consequences of genetic cytochrome P450 2D6 polymorphism. Life Sci 1995; 56: 2285-2298.
22. Coutts RT, Su P, Baker GB. Involvement of CYP2D6, CYP3A4, and other cytochrome P-450 isoenzymes in N-dealkylation reactions. J Pharmacol Tox Meth 1994; 31: 177-186.
23. Kronbach T, Bauer C, Schupke H. Efficient urethane bond cleavage by CYP2D6. 10th International Symposium on Microsomes and Drug Oxidations, Toronto, 1994; P 25.5, (abstract).
24. Caccia S, Conforti I, Duchier J, Garattini S. Pharmacokinetics of fenfluramine and norfenfluramine in volunteers given d- and dl-fenfluramine for 15 days. Eur J Clin Pharmacol 1985; 29: 221-224.
25. Guy-Grand B, Crepaldi G, Lefebvre P, Apfelbaum M, Gries A, Turner P. International trial of long-term dexfenfluramine in obesity. Lancet 1989; ii: 1142-1144.
26. Campbell DB, Gordon BH, Ings RMJ, Richards R, Taylor DW. Factors that may effect the reduction of hunger and body weight following d-fenfluramine administration. Clin Neuropharmacol 1988; 11(suppl 1): S160-S172.