Ibudilast in healthy volunteers: safety, tolerability and pharmacokinetics with single and multiple doses.
Br J Clin Pharmacol
; 66(6): 792-801, 2008 Dec.
Article
em En
| MEDLINE
| ID: mdl-19032723
ABSTRACT
AIMS:
To investigate the safety, tolerability and pharmacokinetics (PK) of ibudilast after a single-dose and a multiple-dose regimen.METHODS:
Healthy adult male (n = 9) and female (n = 9) volunteers were evaluated over a 17-day stay in a Phase 1 unit. Subjects were randomized 1 3 to either oral placebo or ibudilast at 30-mg single administration followed by 14 days of 30 mg b.i.d. Complete safety analyses were performed and, for PK, plasma and urine samples were analysed for ibudilast and its major metabolite.RESULTS:
Ibudilast was generally well tolerated. No serious adverse events occurred. Treatment-related adverse events included hyperhidrosis, headache and nausea. Two subjects discontinued after a few days at 30 mg b.i.d. because of vomiting. Although samples sizes were too small to rule out a sex difference, PK were similar in men and women. The mean half-life for ibudilast was 19 h and median T(max) was 4-6 h. Mean (SD) steady-state plasma C(max) and AUC(0-24) were 60 (25) ng ml(-1) and 1004 (303) ng h ml(-1), respectively. Plasma levels of 6,7- dihydrodiol-ibudilast were approximately 30% of the parent.CONCLUSIONS:
Ibudilast is generally well tolerated in healthy adults when given as a single oral dose of 30 mg followed by 30 mg b.i.d. (60 mg day(-1)) for 14 days. Plasma PK reached steady state within 2 days of starting the b.i.d. regimen. Exposure to ibudilast was achieved of a magnitude comparable to that associated with efficacy in rat chronic pain models.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dor
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Inibidores de Fosfodiesterase
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Piridinas
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Neuropatias Diabéticas
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article