Pharmacokinetic and pharmacodynamic profile following oral administration of the phosphodiesterase (PDE)4 inhibitor V11294A in healthy volunteers

British Journal of Clinical Pharmacology

Volumn 54, Issue 5, 2002, Pages 478-484

  Gale, Donna Donigi ^a   Landells, Linda J ^b   Spina, Domenico ^c   Miller, Alan J ^d   Smith, Kate ^d   Nichols, Terry ^d   Rotshteyn, Yakov ^a   Tonelli, Alfred ^a   Lacouture, Peter ^a   Burch, Ronald M ^a   Page, Clive P ^b,c   O'Connor, Brian J ^c  

^a PURDUE PHARMA L P   (United States)

^b KING'S COLLEGE LONDON   (United Kingdom)

^c KING'S COLLEGE LONDON   (United Kingdom)

^d Napp Pharmaceuticals   (United Kingdom)

Author keywords

Lymphocyte proliferation; Monocytes; PDE4, pharmacokinetics; Thymidine; TNF ; V11294A; Whole blood

Indexed keywords

3 (3 CYCLOPENTYLOXY 4 METHOXYBENZYL) 6 ETHYLAMINO 8 ISOPROPYL 3H PURINE; 3 (3 CYCLOPENTYLOXY 4 METHOXYBENZYL) 8 ISOPROPYL 3H PURIN 6 YLAMINE; DRUG METABOLITE; LIPOPOLYSACCHARIDE; PHOSPHODIESTERASE IV INHIBITOR; PHYTOHEMAGGLUTININ; THYMIDINE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; V 10332;

ADULT; AREA UNDER THE CURVE; ARTICLE; CELL PROLIFERATION; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; CYTOKINE RELEASE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG ELIMINATION; DRUG HALF LIFE; HUMAN; IC 50; IN VITRO STUDY; MALE; MONONUCLEAR CELL; NAUSEA; NORMAL HUMAN; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RASH;

3',5'-CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; ADMINISTRATION, ORAL; ADULT; CELL DIVISION; CROSS-OVER STUDIES; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; HALF-LIFE; HUMANS; MALE; MIDDLE AGED; MONOCYTES; PHOSPHODIESTERASE INHIBITORS; PURINES; TUMOR NECROSIS FACTOR-ALPHA;

EID: 18744362427     PISSN: 03065251     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1365-2125.2002.01682.x     Document Type: Article

References (16)

1. Torphy TJ. Phosphodiesterase isozymes: Molecular targets for novel antiasthma agents. Am J Respir Crit Care Med 1998;157: 351-370.
2. Soderling SH, Beavo JA. Regulation of cAMP and cGMP signaling: New phosphodiesterases and new functions. Curr Opin Cell Biol 2000;12: 174-179.
3. Torphy TJ, Page C. Phosphodiesterases: the journey toward therapeutics. Trends Pharmacol Sci 2000;21: 157-159.
4. Brunnee T, Engelstatter R, Steinijans VW, Kunkel G. Bronchodilatory effect of inhaled zardaverine, a phosphodiesterase III and IV inhibitor, in patients with asthma. Eur Respir J 1992;5: 982-985.
5. Fujimura M, Kamio Y, Saito M, Hashimoto T, Matsuda T. Bronchodilator and bronchoprotective effects of cilostazol in humansin vivo. Am J Respir Crit Care Med 1995;151: 222-225.
6. Foster RW, Rakshi K, Carpenter JR, Small RC. Trials of the bronchodilator activity of the isoenzyme-selective phosphodiesterase inhibitor AH 21-132 in healthy volunteers during a methacholine challenge test. Br J Clin Pharmacol 1992;34: 527-534.
7. Kawasaki A, Hoshino K, Osaki R, Mizushima Y, Yano S. Effect of ibudilast: A novel antiasthmatic agent, on airway hypersensitivity in bronchial asthma. J Asthma 1992;29: 245-252.
8. Bardin PG, Dorward MA, Lampe FC, Franke B, Holgate ST. Effect of selective phosphodiesterase 3 inhibition on the early and late asthmatic responses to inhaled allergen. Br J Clin Pharmacol 1998;45: 387-391.
9. Harbinson PL, MacLeod D, Hawksworth R, et al. The effect of a novel orally active selective PDE4 isoenzyme inhibitor (CDP840) on allergen-induced responses in asthmatic subjects. Eur Respir J 1997;10: 1008-1014.
10. Nell H, Louw C, Leichtl S, Rathgeb F, et al. Acute anti-inflammatory effect of the novel phosphodiesterase 4 inhibitor roflumilast on allergen challenge in asthmatics after a single dose. Am J Respir Crit Care Med 2000;161: A200.
11. Jonker GJ, Tijhuis GJ de Monchey JGR. RP 73401 (a phosphodiesterase IV inhibitor) single does not prevent allergen induced bronchoconstriction during the early phase reaction in asthmatics. Eur Respir J 1996;9: 82s.
12. Nieman RB Fisher BD Amit O Dockhorn RJ. SB 207499 (Ariflo™), a second-generation, selective oral phosphodiesterase type 4 (PDE4) inhibitor, attenuates exercise induced bronchoconstriction in patients with asthma. Am J Respir Crit Care Med 1998;157: A413.
13. Timmer W, Leclerc V, Birraux G, et al. Safety and efficacy of the new PDE4 inhibitor roflumilast administered to patients with excercise-induced asthma over 4 weeks. Am J Respir Crit Care Med 2000;161: A505.
14. Torphy TJ, Barnette MS, Underwood DC, et al. Ariflo™ (SB 207499), a second generation phosphodiesterase 4 inhibitor for the treatment of asthma and COPD, from concept to clinic. Pulm Pharmacol Ther 1999;12: 131-135.
15. Gale DD, Hofer P, Spina D, et al. The pharmacology of a novel phosphodiesterase type 4 inhibitor, V11294A. Pulm Pharmacol Ther 2002; (in press).
16. Spina D, Landells LJ, Page CP. The role of phosphodiesterase isoenzymes in health and in atopic disease. In Advances in Pharmacology, ed. August T. San Diego: Academic Press Inc, 1998: 33-89.