Blood quinidine levels and cardiac effects in white British and Nigerian subjects.

Olatunde, A. O.; Da, Evans

doi:10.1111/j.1365-2125.1982.tb02022.x

Cited by 13 publications

(12 citation statements)

References 9 publications

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“…this is subsequently transferred to the simulation and results in a large difference between the free and total concentration scenarios. Similar effects can be observed for the Olatunde study (Olatunde and Price Evans, 1982), where the concentrations are comparable to those in the work of el-eraky. there is a difference of up to 30 ms in the ΔQTc between free and total scenarios, although it this connected with an underprediction of the plasma concentration in the Olatunde study, which aligns and mitigates the PD effect and makes it less spectacular.…”

Section: Results Presented Insupporting

confidence: 85%

“…the study inclusion criteria were: a) healthy Caucasian volunteers, b) availability of information about the quinidine pharmacokinetics, ideally presented as a drug plasma concentration change in time, c) PD results presented as Qt/ QTc or ΔQT/ΔQTc (regardless of the correction type), thus comparable with the simulation outputs. Nine papers fulfilling such conditions were identified and used for the study (Belz et al, 1982;Ching et al, 1991;El-Eraky and Thomas, 2003;Fieldman et al, 1977;Kaukonen et al, 1997;laganiere et al, 1996;Min et al, 1996;Olatunde and Price Evans, 1982;Shin et al, 2007). Characteristics of the clinical studies derived from the identified papers are presented in Table 1.…”

Section: Datamentioning

confidence: 99%

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In vitro to human in vivo translation – pharmacokinetics and pharmacodynamics of quinidine

Polak

2013

ALTEX

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SummaryThe translational sciences aim to transfer results from basic research to the treatment of animals or patients. One of the approaches that could be utilized to achieve this goal is the in vitro-in vivo extrapolation (IVIVE) concepts of PK and PD mechanistic modeling and simulation to highlight the importance of assessing drug effect and safety in the preliminary phases of the drug development process. the IVIVe application approach necessitates the provision of three data sets: 1) drug related (ADMe processes and activity), 2) system data (describing population and variability of the chosen parameters), and 3) simulated trial design (Rostami-Hodjegan and tucker, 2007). the IVIVe methodology is a robust evaluation tool that assesses inter-individual variability based on the virtual population characteristics in the population study group.to assess the application value of the described approach, quinidine was selected as the model drug in the virtual study described here. the study endpoints covered plasma concentration of the parent compound and its main metabolite, 3-OH quinidine, from the pharmacokinetic side. either Qtc interval or the drug triggered change as compared to the baseline (ΔQT/ ΔQTc) were used as the pharmacodynamic effect descriptors. this pharmacodynamic effect dictates that drug cardiac safety should be regarded as a pivotal focal point of this study. Preclinical studies routinely use in vitro approaches to assess cardiac safety; however, non-rodent species (e.g., dogs, monkeys) are commonly used in the assessment procedure. this study proposes a novel concept based on a combination of mechanistic PBPK/PD modeling and simulation to predict the cardiac effects of drugs and thus help to incorporate the 3Rs concept

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Section: Results Presented Insupporting

confidence: 85%

Section: Datamentioning

confidence: 99%

In vitro to human in vivo translation – pharmacokinetics and pharmacodynamics of quinidine

Polak

2013

ALTEX

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“…There are relatively few data on interethnic differences in drug‐induced QT prolongation. Olatunde & Price Evans examined the relationship between serum quinidine concentrations and cardiac effects in white British and Nigerian subjects [17]. They reported that quinidine concentrations in white British subjects tended to be lower than those in Nigerians, yet the quinidine‐induced QTc increase was greater in white British subjects than in Nigerians.…”

Section: Discussionmentioning

confidence: 99%

Possible interethnic differences in quinidine‐induced QT prolongation between healthy Caucasian and Korean subjects

Shin

Kang

Shon

et al. 2006

Brit J Clinical Pharma

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AimsThe aim of this study was to evaluate the pharmacokinetics and pharmacodynamics of quinidine-induced QT prolongation in healthy Caucasian and Korean subjects to investigate interethnic differences in susceptibility to drug-induced arrhythmia. MethodsA randomized, double-blind crossover study was conducted in 24 (12 male and 12 female) Korean and 13 (seven male and six female) Caucasian subjects. After a 20 min infusion of quinidine (4 mg kg -1 ) or saline, the serum concentration of quinidine and the QT interval corrected by Bazett's formula (QTc) were monitored. The dynamic data were analyzed by means of a population modelling approach using NONMEM. ResultsThere were no statistical differences in the pharmacokinetic profiles of quinidine between ethnic groups. The QTc values in Caucasians were higher than those in Koreans at the same quinidine concentrations, especially at higher quinidine concentrations and in female subjects. According to an Emax model E E E E Δ max , the population modelling approach revealed that E0 (ms) was related to gender (408 + [34*(1 -Sex)]; 1 for male and 0 for female), DEmax (ms) was related to ethnicity ((136* fETHN) + Cfemale: fETHN = 1 for Koreans and 1.26 for Caucasians; Cfemale was 106 only for Caucasian females), and EC50 was estimated to be 3.13 mm. ConclusionsThese results suggest that Korean subjects were less sensitive to quinidine-induced QT prolongation than Caucasian subjects, and that this trend was particularly true for females. Further population-based studies are merited to characterize more completely the ethnic differences in drug-induced QT prolongation between Asians and other ethnic groups.

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“…There are relatively few data on interethnic differences in druginduced QT prolongation (Olatunde and Price Evans 1982;Shin et al 2006). It is reported that quinidine concentrations in white British subjects tended to be lower than those in Nigerians, yet the quinidine-induced QTc increase was greater in white British subjects than in Nigerians (Olatunde and Price Evans 1982). Also, it is suggested that Korean subjects are less sensitive to quinidine-induced QTc prolongation than Caucasian subjects (Shin et al 2006).…”

Section: Resultsmentioning

confidence: 95%

“…These determinants might lead to differences in the basic pattern and/or drug-induced QTc changes. There are relatively few data on interethnic differences in druginduced QT prolongation (Olatunde and Price Evans 1982;Shin et al 2006). It is reported that quinidine concentrations in white British subjects tended to be lower than those in Nigerians, yet the quinidine-induced QTc increase was greater in white British subjects than in Nigerians (Olatunde and Price Evans 1982).…”

Section: Resultsmentioning

confidence: 98%

Genetic Polymorphism of Glutathione S-transferase T1 (GSTT1) and QT-Interval in Schizophrenia Patients

2009

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Several antipsychotic agents are known to prolong the QT interval in a dose-dependent manner. The antipsychotic drugs are substrates of the phase I of biotransformation enzymes of cytochrome P450. In order to find the possible influence of polymorphism of GSTT1 (a member of class theta glutathione S-transferase) on rate-corrected QT interval (QTc) of schizophrenia patients, the present study was done. Forty-three schizophrenia in-patients participated in the study. The patients were diagnosed as chronic schizophrenia according to structured clinical interview using SCID-I (clinician version) to confirm and document DSM-IV diagnosis. Measurements of QT and RR intervals were recorded using a magnifying grid on lead II. The QTc was calculated according to Bazett's formula. Polymerase chain reaction-based method was used in order to determine the GSTT1 genotypes. Based on the fitted model of multiple linear regression analysis, QTc decreased in persons with positive GSTT1 genotype in comparison with the null genotype (beta = -0.328, t = -2.346, p = 0.024). Active genotype of GSTT1 decreased the QTc. Also, QTc was significantly associated with smoking status; it was decreased in smokers compared with nonsmokers (beta = -0.372, t = -2.372, p = 0.014).

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Blood quinidine levels and cardiac effects in white British and Nigerian subjects.

Cited by 13 publications

References 9 publications

In vitro to human in vivo translation – pharmacokinetics and pharmacodynamics of quinidine

In vitro to human in vivo translation – pharmacokinetics and pharmacodynamics of quinidine

Possible interethnic differences in quinidine‐induced QT prolongation between healthy Caucasian and Korean subjects

Genetic Polymorphism of Glutathione S-transferase T1 (GSTT1) and QT-Interval in Schizophrenia Patients

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