Amisulpride: Real-World Evidence of Dose Adaptation and Effect on Prolactin Concentrations and Body Weight Gain by Pharmacokinetic/Pharmacodynamic Analyses

Glatard, Anaïs; Guidi, Monia; Delacrétaz, Aurélie; Dubath, Céline; Grosu, Claire; Laaboub, Nermine; Gunten, Armin von; Conus, Philippe; Csajka, Chantal; Eap, Chin B.

doi:10.1007/s40262-019-00821-w

Cited by 10 publications

(7 citation statements)

References 32 publications

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“…Our study screened covariates with high standards ( P < 0.001) and found that the most significant was the θ CL-AGE as increasing age decreased amisulpride elimination. In agreement with this, Glatard, A et al 11 reported that LBW was also a significant covariate for the CL/F of amisulpride. LBW with an allometric exponent of ~2/3 may be most suitable for describing an increase in CL with body size as it accounts for both body composition and allometric scaling principles concerning differences in metabolic rates across size.…”

Section: Discussionsupporting

confidence: 71%

“… 23 Amisulpride is also a substrate of the P-glycoprotein (P-gp) transporter. 24 Moreover, Glatard, A et al 11 proved that OCT1 and OCT2 transporters, the P-glycoprotein, and some nuclear factors had no significant influence on the clearance of amisulpride. Therefore, amisulpride did not need to be adjusted according to genotype and transporters.…”

Section: Discussionmentioning

confidence: 99%

“… 10 One study in Caucasian adult patients investigated the effects of concomitant medications, genetic polymorphisms (such as the OCT1, OCT2 transporters, P-glycoprotein and some nuclear factors), age and lean body weight (LBW) on amisulpride concentration and included age and LBW in the final model. 11 Another study in older people and Alzheimer’s disease found that age and body weight significantly affected amisulpride clearance at low dose (25–75 mg daily). 12 In addition, two studies reported a higher dose-adjusted concentrations (C/D, the ratio of drug concentration to dose under steady-state and trough conditions) in elderly patients, 13 , 14 which showed that age is most likely to be the major influence on amisulpride.…”

Section: Introductionmentioning

confidence: 99%

“…9 PPK analysis has previously been applied to drugs with high IIV. 10 One study in Caucasian adult patients investigated the effects of concomitant medications, genetic polymorphisms (such as the OCT1, OCT2 transporters, P-glycoprotein and some nuclear factors), age and lean body weight (LBW) on amisulpride concentration and included age and LBW in the final model. 11 Another study in older people and Alzheimer's disease found that age and body weight significantly affected amisulpride clearance at low dose (25-75 mg daily).…”

Section: Introductionmentioning

confidence: 99%

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Modeling and Simulation for Individualized Therapy of Amisulpride in Chinese Patients with Schizophrenia: Focus on Interindividual Variability, Therapeutic Reference Range and the Laboratory Alert Level

Huang

Wang

et al. 2021

DDDT

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Purpose To explain the high inter-individual variability (IIV) and the frequency of exceeding the therapeutic reference range and the laboratory alert level of amisulpride, a population pharmacokinetic (PPK) model in Chinese patients with schizophrenia was built based on therapeutic drug monitoring (TDM) data to guide individualized therapy. Patients and Methods Plasma concentration data (330 measurements from 121 patients) were analyzed using a nonlinear mixed-effects modeling (NONMEM) approach with first-order conditional estimation with interaction (FOCE I). The concentrations of amisulpride were detected by HPLC-MS/MS. Age, weight, sex, combination medication history and renal function status were evaluated as main covariates. The model was internally validated using goodness-of-fit, bootstrap and normalized prediction distribution error (NPDE). Recommended dosage regimens for patients with key covariates were estimated on the basis of Monte Carlo simulations and the established model. Results A one-compartment model with first-order absorption and elimination was found to adequately characterize amisulpride concentration in Chinese patients with schizophrenia. The population estimates of the apparent volume of distribution (V/F) and apparent clearance (CL/F) were 12.7 L and 1.12 L/h, respectively. Age significantly affected the clearance of amisulpride and the final model was as follows: CL/F=1.04×(AGE/32) −0.624 (L/h). To avoid exceeding the laboratory alert level (640 ng/mL), the model-based simulation results showed that the recommended dose of amisulpride was no more than 600 mg/d for patients aged 60 years, 800 mg/d for those aged 40 years and 1200 mg/d for those aged 20 years, respectively. Conclusion Dosage optimization of amisulpride can be carried out according to age to reduce the risk of adverse reactions. The model can be used as a suitable tool for designing individualized therapy for Chinese patients with schizophrenia.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Modeling and Simulation for Individualized Therapy of Amisulpride in Chinese Patients with Schizophrenia: Focus on Interindividual Variability, Therapeutic Reference Range and the Laboratory Alert Level

Huang

Wang

et al. 2021

DDDT

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“…Although the incidence of adverse effects of amisulpride is reported to be low, optimizing dosing regimens and suppressing concentration uctuation using a PPK model might maximize the therapeutic effect of the drug and reduce its adverse effects. To date, several reports have described PPK models of amisulpride to guide dose adjustments 14,15 . However, little data have been reported for adult Chinese patients with schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Effect of the dose regimen on the serum amisulpride concentration and simulation of concentration reference ranges based on population pharmacokinetics

Li¹,

Li²,

Huang³

et al. 2021

Preprint

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Aims This study aims to determine the factors associated the large variability and provided the concentrations reference ranges for different dose ranges. Methods A retrospective study was conducted in a psychiatric hospital. The factors associated with the serum amisulpride concentration were examined using multiple linear regression analysis. A comparison of serum amisulpride concentrations among different dose regimens was conducted via analysis of covariance. The amisulpride concentration range for different dosing regimens was simulated using the population pharmacokinetics of Chinese patients with schizophrenia using the Monte Carlo method. Results In total, 472 samples from 291 patients were examined to determine the factors associated with amisulpride concentrations. Multiple linear regression analysis indicated that age and the daily dose were positively correlated with the serum drug concentration, whereas male gender and sampling time before the last administration were negative correlated with its concentration. The serum amisulpride concentration significantly differed among the dose regimens. Using an established amisulpride population pharmacokinetic model, the simulated trough concentrations exceeded 320 ng/mL for most regimens with daily doses greater than 600 mg/day. Conclusion Differences in dose regimens and daily doses contributed to the large variation of the serum amisulpride concentration. The currently recommended reference does not ensure the attainment of appropriate therapeutic concentrations.

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Bioequivalence of 200 mg Amisulpride Tablets in Healthy Chinese Volunteers under Fasting and Fed Conditions

Cao,

2023

Clinical Pharm in Drug Dev

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In this study, we compared the pharmacokinetics and safety of a new generic product and a branded reference product of amisulpride tablets. Additionally, we assessed the bioequivalence of the 2 products in healthy Chinese volunteers to acquire sufficient evidence for the marketing approval of the generic drug. Thirty volunteers under fasting and fed conditions were randomly administered a single dose of the test or reference drug orally, followed by a 7‐day washout period. The pharmacokinetic parameters were obtained by the concentration‐time profiles, including the area under the plasma concentration‐time curve (AUC) over the dosing interval, AUC from time zero to infinity, maximum plasma concentration, time to achieve maximum plasma concentration, and elimination half‐life. AUC from time zero to infinity of amisulpride in the postprandial group was reduced by approximately 25%, suggesting that a high‐fat diet can affect this parameter. In the aspect of safety, no serious adverse events occurred. This study demonstrated that generic and reference products of amisulpride tablets were bioequivalent in healthy Chinese volunteers under fasting and fed conditions.

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Amisulpride: Real-World Evidence of Dose Adaptation and Effect on Prolactin Concentrations and Body Weight Gain by Pharmacokinetic/Pharmacodynamic Analyses

Cited by 10 publications

References 32 publications

Modeling and Simulation for Individualized Therapy of Amisulpride in Chinese Patients with Schizophrenia: Focus on Interindividual Variability, Therapeutic Reference Range and the Laboratory Alert Level

Modeling and Simulation for Individualized Therapy of Amisulpride in Chinese Patients with Schizophrenia: Focus on Interindividual Variability, Therapeutic Reference Range and the Laboratory Alert Level

Effect of the dose regimen on the serum amisulpride concentration and simulation of concentration reference ranges based on population pharmacokinetics

Bioequivalence of 200 mg Amisulpride Tablets in Healthy Chinese Volunteers under Fasting and Fed Conditions

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