Bioequivalence of a Slow-Release and a Non-Retard Formulation of Isradipine

Holmes, David; Kutz, K

doi:10.1093/ajh/6.3.70s

Cited by 12 publications

(14 citation statements)

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“…35 To minimize reflex tachycardia due to hypotension, associated with isradipine's immediate-release preparation, we administered isradipine's SR formulation at a dose of 30 mg, which achieves about the same peak central effect without inducing tachycardia. 36 We set the low-dose of SR isradipine (15 mg) at half the maximum dose to provide a pharmacologically relevant dosing range for experimentation. Isradipine tablets obtained from Sandoz Corporation were overencapsulated in royal blue size 0 capsules (Shionogi Qualicaps) and filled with cornstarch.…”

Section: Choice Of Medication Dose and Its Preparationmentioning

confidence: 99%

Effects of Isradipine on Cocaine-Induced Subjective Mood

Johnson

Roache²,

Ait-Daoud

et al. 2004

Journal of Clinical Psychopharmacology

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We hypothesized that in humans, as in animals, isradipine, a dihydropyridine-class calcium channel antagonist, would antagonize cocaine's rewarding effects, based on preclinical evidence that isradipine inhibits cocaine-mediated increases in mesolimbic dopamine (DA), thereby reducing cocaine's abuse liability. Confirmation of our hypothesis would make isradipine a promising medication for treating cocaine dependence. Eighteen male and female volunteers (mean age, 32.6 years) who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for cocaine dependence participated in a double-blind, placebo-controlled, crossover study. Subjects received placebo or sustained-release (SR) low-dose or high-dose isradipine (15 or 30 mg), plus placebo or low-dose or high-dose cocaine HCl (0.325 or 0.650 mg/kg), for 9 treatment sessions separated by a 2-day interval. Standardized assessments of abuse liability, including a choice procedure to determine preference for cocaine with and without isradipine over monetary incentives, were conducted at scheduled intervals. Cocaine administration produced dose-related prototypic increases in stimulant-related effects, including euphoria, and drug preference over monetary incentives. Isradipine lacked any stimulant or abuse liability effects or the propensity to elicit craving, and it did not antagonize any of cocaine's stimulant-related effects associated with its abuse liability. In conclusion, SR isradipine (up to 30 mg) does not antagonize cocaine's rewarding effects in cocaine-dependent individuals. While higher isradipine doses may have been more effective at antagonizing cocaine reward, we could not test such doses due to the risk of serious adverse events. Also, isradipine-mediated inhibition of mesolimbic DA release may be an ineffective treatment of cocaine dependence.

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Section: Choice Of Medication Dose and Its Preparationmentioning

confidence: 99%

Effects of Isradipine on Cocaine-Induced Subjective Mood

Johnson

Roache²,

Ait-Daoud

et al. 2004

Journal of Clinical Psychopharmacology

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“…On the other hand, the peak concentration ( C max ) and time to reach it ( t max ) of sustained‐release isradipine of 30 mg dosage in Johnson et al . 's () study were comparable to those reported after a 5 mg dosage administration of the sustained‐release isradipine (Holmes and Kutz, ). These results indicate that the discrepancies in pharmacokinetic parameters are substantial.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic properties of isradipine after single‐dose and multiple‐dose oral administration in Chinese volunteers: a randomized, open‐label, parallel‐group phase I study

Wang

Jin

Wang

et al. 2013

Biomedical Chromatography

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Isradipine could be used for the treatment of high blood pressure or Parkinsonism, yet the study on pharmacokinetics (PK) of isradipine is lacking in the Chinese population. The current study aims to assess the dose proportionality, pharmacokinetics and gender effect of isradipine following oral single and multiple doses in Chinese subjects. A randomized, open-label, parallel-group trial was conducted in 30 healthy Chinese volunteers. Subjects randomly received a single dose of 2.5, 5 or 10 mg, and multiple doses (2.5 mg) of isradipine. Blood samples were collected pre-dose (0 h) and 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, 36 and 48 h post-dose. Isradipine was rapidly absorbed with the time to maximum concentration <1.27 h for all dosage groups. The maximum concentrations were 2.46, 5.34, 10.93 and 3.32 ng/mL and area under the concentration-time curve from time zero to the last time point (AUClast ) were 7.05, 12.58, 24.68 and 5.31 ng/ml · h for the 2.5, 5 and 10 mg single-dose and 2.5 mg multiple-dose groups, respectively. The half-life ranged from 5.76 to 7.94 h. The maximum concentration and AUC were found to increase linearly and dose-dependently for isradipine. No statistical gender differences were found. These findings indicated that the pharmacokinetic parameters of isradipine in Chinese population were dose-proportional and predictable over a range of 2.5-10 mg isradipine oral doses.

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“…Since a 90% CI for C max and AUCs ratios were ranging within the limits of the FDA (80-125%), it was determined that the two types of 5 mg SR isradipine formulations were considered to be bioequivalent. In previous reports, absorption of an orally administrated IR isradipine capsule in the fasting condition was rapid with 1.2-2.0 h of T max and 6.1-13.8 h of elimination half-life (T 1/2 ) [16][17][18]21]. SR isradipine capsules took about 3-4 times longer (6 h) for the T max compared to IR isradipine.…”

Section: Clinical Pharmacokinetic and Bioequivalence Study In Healthymentioning

confidence: 93%

“…The pharmacokinetics of isradipine have been reported following oral administration of immediate-release (IR) isradipine or sustained-release (SR) isradipine in healthy volunteers [16][17][18][19], cardiac patients [20], and cocaine-dependent individuals [21]. At an oral dose ranging between 2.4-20 mg, the pharmacokinetics of isradipine appeared to be linear [16,17].…”

Section: Introductionmentioning

confidence: 99%