Influence of CYP2D6 gene polymorphisms on the pharmacokinetics of aripiprazole in healthy Chinese subjects

2021 ◽  
Author(s):  
Xiaodan Zhang ◽  
Chengquan Liu ◽  
Shuang Zhou ◽  
Ran Xie ◽  
Xu He ◽  
...  
Keyword(s):  
Chinese Patients ◽  
Cyp2d6 Gene ◽  
Time Curve ◽  
Concentration Time ◽  
Significant Difference ◽  
Liquid Chromatography Tandem Mass ◽  
Intermediate Metabolizer ◽  
Cyp2d6 Polymorphisms ◽  
Chinese Subjects ◽  
Intermediate Metabolizers

Background: Pharmacogenetics study was added into 2 bioequivalence trials of aripiprazole. The correlation between CYP2D6 polymorphisms and aripiprazole pharmacokinetics (PK) was analyzed. Materials & methods: A total of 140 subjects were included. A total of 26 CYP2D6 gene alleles were detected. The plasma concentration of aripiprazole was measured by liquid chromatography-tandem mass spectrometry (LC–MS/MS). SPSS Statistics 21 was used to analyze the correlation between CYP2D6 polymorphisms and aripiprazole PK parameters. Results: All of the four PK parameters were significantly influenced by CYP2D6 rs1058164 and rs28371699. t1/2 and area under the concentration-time curve (AUC0–∞) exhibited significant difference between CYP2D6 extensive metabolizers and intermediate metabolizers. Conclusion: Aripiprazole PK was greatly influenced by CYP2D6. Attention should be paid to the possible dose adjustment for CYP2D6 intermediate metabolizer population when the drug is used in Chinese patients.

scholarly journals PHARMACODYNAMICS EFFECT OF METHYLPREDNISOLONE TABLETS ON THE SERUM CONCENTRATION OF ANNEXIN A1: IN VIVO COMPARATIVE STUDY BETWEEN GENERIC AND INNOVATOR DRUG

2019 ◽  
Vol 12 (1) ◽  
pp. 414
Author(s):  
Hansen Nasif ◽  
Henny Lucida ◽  
Yanwirasti Yanwirasti ◽  
Yufri Aldi ◽  
Yori Yuliandra
Keyword(s):  
Serum Concentration ◽  
Peak Concentration ◽  
Peak Time ◽  
Annexin A1 ◽  
Onset Of Action ◽  
Time Curve ◽  
Concentration Time ◽  
Significant Difference ◽  
Generic Products

Objective: The aims of this study were to investigate the comparative pharmacodynamics effect of methylprednisolone (MP) innovator, MP branded generic, and MP generic products to the serum concentration of annexin A1 (AnxA1).Methods: It was conducted by two-way crossover design in male rabbits. AnxA1 was measured at 0, 0.5, 1, 2, 3, 5, 7, and 9 h after the administration of the drugs. The peak concentration (Cmax), the time at which the peak concentration was achieved (Tmax), and the area under the plasma concentration-time curve (AUC) were also determined.Results: The highest concentration and widest AUC of AnxA1 were obtained in MP innovator drug. MP innovator and branded generic reaches the peak time (Tmax) at the third 3rd h, while the MP generic reaches the peak time at the 5th h. The results showed that there was no significant difference in the serum concentration of AnxA1 between MP tablets after analyzed with a one-way analysis of variance.Conclusion: It could be concluded that the innovator drug of MP tablet gave the same effect on the serum concentration of AnxA1 than its generic counterparts, but an onset of action MP innovator and branded generic is faster than the generic product.

Lack of Acipimox-Digoxin Interaction in Patient Volunteers

1992 ◽  
Vol 11 (5) ◽  
pp. 357-359 ◽  
Author(s):  
Chioli Pascal Chijioke ◽  
Richard Martin Pearson ◽  
Strolin Benedetti
Keyword(s):  
Oral Absorption ◽  
Human Subjects ◽  
Plasma Concentrations ◽  
Time Curve ◽  
Digoxin Interaction ◽  
Concentration Time ◽  
Elimination Half ◽  
Significant Difference ◽  
Before And After ◽  
Renal Clearances

1 A study was carried out to find out if digoxin and acipimox interact. 2 Six elderly patients on digoxin were each given acipimox 150 mg three daily for a week, after informed consent. Digoxin and acipimox plasma concentrations and urinary excretion were measured after the first dose of acipimox and after a week of treatment. 3 Data were fitted to a one-compartment oral absorption model. Areas under the plasma concentration-time curve, plasma and renal clearances, and elimination half-life were computed. 4 There was no significant difference in digoxin plasma concentrations and kinetic parameters before and after acipimox administration. Acipimox kinetics were not affected by the concomitant ingestion of digoxin. 5 The patients' clinical condition remained stable during the study. 6 Thus there was no evidence for an adverse interaction between digoxin and acipimox in human subjects under the conditions of this study.

scholarly journals Penetration of Ciprofloxacin into the Interstitial Space of Inflamed Foot Lesions in Non-Insulin-Dependent Diabetes Mellitus Patients

1999 ◽  
Vol 43 (8) ◽  
pp. 2056-2058 ◽  
Author(s):  
Markus Müller ◽  
Martin Brunner ◽  
Ursula Hollenstein ◽  
Christian Joukhadar ◽  
Rainer Schmid ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Time Curve ◽  
Concentration Time ◽  
Significant Difference ◽  
Tissue Area ◽  
Insulin Dependent ◽  
Foot Lesions

ABSTRACT Interstitial ciprofloxacin concentrations were measured by microdialysis in inflamed foot lesions of non-insulin-dependent diabetes mellitus patients following intravenous administration of 0.2 g of ciprofloxacin. Interstitial ciprofloxacin concentrations were significantly lower than corresponding serum concentrations. There was no significant difference in the penetration of ciprofloxacin into inflamed and unaffected tissue (area under the concentration-time curveinfection/area under the concentration-time curveunaffected tissue = 0.99 ± 0.15 [mean ± standard error], n = 6). Thus, inflammation appears to have little or no effect on the penetration of ciprofloxacin into tissue.

scholarly journals Effects of Silymarin on the In Vivo Pharmacokinetics of Simvastatin and Its Active Metabolite in Rats

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1666
Author(s):  
Ying Li ◽  
Yin Wu ◽  
Ya-Jing Li ◽  
Lu Meng ◽  
Cong-Yang Ding ◽  
...  
Keyword(s):  
Active Metabolite ◽  
Compartmental Model ◽  
Elimination Rate ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Simultaneous Quantification ◽  
Concentration Time ◽  
Significant Difference ◽  
In Vivo Pharmacokinetics

Herein, the effect of silymarin pretreatment on the pharmacokinetics of simvastatin in rats was evaluated. To ensure the accuracy of the results, a rapid and sensitive UPLC–MS/MS method was established for simultaneous quantification of simvastatin (SV) and its active metabolite simvastatin acid (SVA). This method was applied for studying the pharmacokinetic interactions in rats after oral co-administration of silymarin (45 mg/kg) and different concentrations of SV. The major pharmacokinetic parameters, including Cmax, tmax, t1/2, mean residence time (MRT), elimination rate constant (λz) and area under the concentration-time curve (AUC0–12h), were calculated using the non-compartmental model. The results showed that the co-administration of silymarin and SV significantly increased the Cmax and AUC0–12h of SVA compared with SV alone, while there was no significant difference with regards to Tmax and t1/2. However, SV pharmacokinetic parameters were not significantly affected by silymarin pretreatment. Therefore, these changes indicated that drug-drug interactions may occur after co-administration of silymarin and SV.

scholarly journals Pharmacokinetics of Florfenicol in Healthy Pigs and in Pigs Experimentally Infected with Actinobacillus pleuropneumoniae

2003 ◽  
Vol 47 (2) ◽  
pp. 820-823 ◽  
Author(s):  
Jianzhong Liu ◽  
Ki-Fai Fung ◽  
Zhangliu Chen ◽  
Zhenling Zeng ◽  
Jie Zhang
Keyword(s):  
Half Life ◽  
Clinical Signs ◽  
Actinobacillus Pleuropneumoniae ◽  
Pharmacokinetic Parameters ◽  
X Rays ◽  
Time Data ◽  
Time Curve ◽  
Chromatography Method ◽  
Concentration Time ◽  
Significant Difference

ABSTRACT A comparative in vivo pharmacokinetic study of florfenicol was conducted in 18 crossbred pigs infected with Actinobacillus pleuropneumoniae following intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration of a single dose of 20 mg/kg. The disease model was confirmed by clinical signs, X rays, pathohistologic examinations, and organism isolation. Florfenicol concentrations in plasma were determined by a validated high-performance liquid chromatography method with UV detection at a wavelength of 223 nm. Pharmacokinetic parameters were calculated by using the MCPKP software (Research Institute of Traditional Chinese Veterinary Medicine, Lanzhou, China). The disposition of florfenicol after a single i.v. bolus was described by a two-compartment model with values for the half-life at α phase (t 1/2α), the half-life at β phase (t 1/2β), the area under the concentration-time curve (AUC0-∞), and the volume of distribution at steady state (V ss) of 0.37 h, 2.91 h, 64.86 μg · h/ml, and 1.2 liter/kg, respectively. The concentration-time data fitted the one-compartment (after i.m.) and two-compartment (after p.o.) models with first-order absorption. The values for the maximum concentration of drug in serum (C max), t 1/2α, t 1/2β, and bioavailability after i.m. and p.o. dosing were 4.00 and 8.11 μg/ml, 0.12 and 3.91 h, 13.88 and 16.53 h, and 122.7 and 112.9%, respectively, for the two models. The study showed that florfenicol was absorbed quickly and completely, distributed widely, and eliminated slowly in the infected pigs, and there was no statistically significant difference between the pharmacokinetic profiles for the infected and healthy pigs.

Different Underlying Mechanism Might Explain the Absence of a Significant Difference in Area Under the Concentration–Time Curve of Linezolid for Different ABCB1 Genotypes

2019 ◽  
Vol 41 (2) ◽  
pp. 253-254 ◽  
Author(s):  
Mathieu S. Bolhuis ◽  
Onno W. Akkerman ◽  
Marieke G. G. Sturkenboom ◽  
Wiel C. M. de Lange ◽  
Tjip S. van der Werf ◽  
...  
Keyword(s):  
Underlying Mechanism ◽  
Time Curve ◽  
Concentration Time ◽  
Significant Difference

Pharmacokinetic Study on Protocatechuic Aldehyde and Hydroxysafflor Yellow A of Danhong Injection in Rats with Hyperlipidemia

Pharmacology ◽  
2018 ◽  
Vol 102 (3-4) ◽  
pp. 154-160 ◽  
Author(s):  
Jing Zhou ◽  
Min Li ◽  
Weifeng Jin ◽  
Xiaohong Li ◽  
Hongjin Fan ◽  
...  
Keyword(s):  
Drug Combination ◽  
Combination Group ◽  
Hydroxysafflor Yellow A ◽  
Time Curve ◽  
Danhong Injection ◽  
Concentration Time ◽  
Protocatechuic Aldehyde ◽  
Significant Difference ◽  
Group 16 ◽  
Combined Medication

Background: Protocatechuic aldehyde (PAL) and hydroxysafflor yellow A (HSYA) are 2 effective ingredients of Danhong Injection, which is extensively used for the clinical treatment of cardio-cerebrovascular diseases. This study aims to investigate the pharmacokinetic differences between single and combined medication of PAL and HSYA and analyze the interaction of the above effective components in hyperlipidemia rats. Methods: Thirty male SD rats were randomly divided into the control group (n = 6) and the model group (n = 24). The hyperlipidemia model was established by feeding with superfatted forage. The successful model rats were then randomly divided into the PAL group (16 mg/kg), the HSYA group (10 mg/kg), and the combination group (16 mg/kg + 10 mg/kg). Administration through tail-vein, and orbital blood was sampled at different time points. The mass concentration of PAL and HSYA was determined by high performance liquid chromatography (HPLC-DAD). Analysis of pharmacokinetic parameters was conducted by using DAS 3.2.6 software and SPSS 19.0 statistical analysis software. Results: According to the parameters of statistical moment of non-compartmental model, there was a significant difference in plasma clearance (CL) between the PAL group and the drug combination group (p < 0.01), as well as in the area under the first moment of the plasma concentration-time curve and the elimination half-life (t1/2) between the HSYA group and the drug combination group (p < 0.01) but no obvious differences about the blood concentration time curve area, the average dwell time (MRT), and the peak concentration (Cmax; p > 0.05). Conclusion: The combined medication of PAL and HSYA could increase the plasma CL significantly and have a great influence on the absorption of HSYA in rats with hyperlipidemia.

scholarly journals Pilot Pharmacokinetic Study of Human Immunodeficiency Virus-Infected Patients Receiving Tenofovir Disoproxil Fumarate (TDF): Investigation of Systemic and Intracellular Interactions between TDF and Abacavir, Lamivudine, or Lopinavir-Ritonavir

2009 ◽  
Vol 53 (5) ◽  
pp. 1937-1943 ◽  
Author(s):  
Alain Pruvost ◽  
Eugènia Negredo ◽  
Frédéric Théodoro ◽  
Jordi Puig ◽  
Mikaël Levi ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Pharmacokinetic Parameters ◽  
Reverse Transcriptase Inhibitors ◽  
Plasma Exposure ◽  
Time Curve ◽  
Residual Concentration ◽  
Concentration Time ◽  
Immunodeficiency Virus ◽  
Liquid Chromatography Tandem Mass

ABSTRACT Previous work has demonstrated the existence of systemic interaction between tenofovir (TFV) disoproxil fumarate (TDF) and didanosine as well as between TDF and lopinavir-ritonavir (LPV/r). Here we investigated TDF interactions with the nucleoside reverse transcriptase inhibitors (NRTIs) lamivudine (3TC) and abacavir (ABC), comparing both the concentrations of nucleoside/nucleotide reverse transcriptase inhibitors in plasma and the intracellular concentrations of their triphosphate metabolites (NRTI-TP) for human immunodeficiency virus-infected patients receiving these NRTIs with TDF and after 4 weeks of TDF interruption. We also looked at interactions between TDF-ABC and LPV/r, comparing patients receiving or not receiving LPV/r. Blood samples were taken at baseline and at 1, 2, and 4 h after dosing. Liquid chromatography-tandem mass spectrometry was used to measure NRTIs and NRTI-TPs. Statistical analyses were performed on pharmacokinetic parameters: the area under the concentration-time curve from 0 to 4 h (AUC0-4), the maximum concentration of the drug (C max), and the residual concentration of the drug at the end of the dosing interval (C trough) for plasma and the AUC0-4 and C trough for intracellular data. Among the groups of patient discontinuing TDF, the very long intracellular half-life of elimination (150 h) of TFV-DP (the diphosphorylated metabolite of TFV, corresponding to a triphosphorylated species) was confirmed. Comparison between groups as well as the longitudinal study showed no significant systemic or intracellular interaction between TDF and ABC or 3TC. Significant differences were observed between patients receiving LVP/r and those receiving nevirapine. For ABC, plasma exposure was decreased (40%) under LVP/r, while, in contrast, plasma exposure to TFV was increased by 50% and the intracellular TFV-DP AUC0-4 was increased by 59%. A trend for a gender effect was observed for TFV-DP at the intracellular level, with higher and C trough values for women.

Influence of Hypovolemia on the Pharmacokinetics and Electroencephalographic Effect of γ-Hydroxybutyrate in the Rat

2002 ◽  
Vol 97 (5) ◽  
pp. 1218-1226 ◽  
Author(s):  
Diederik K. Van Sassenbroeck ◽  
Peter De Paepe ◽  
Frans M. Belpaire ◽  
Paul A. Boon ◽  
Walter A. Buylaert
Keyword(s):  
Blood Pressure ◽  
High Performance ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Control Procedure ◽  
Time Data ◽  
Time Curve ◽  
Concentration Time ◽  
Gamma Hydroxybutyrate ◽  
Significant Difference

Background Hypovolemia alters the effect of propofol in the rat by influencing the pharmacokinetics and the end organ sensitivity. We now studied the effect of hypovolemia on the anesthetic gamma-hydroxybutyrate (GHB) because in contrast with propofol it increases blood pressure. Methods Thirty-two rats were randomly assigned to undergo moderate hypovolemia or a control procedure. Each rat received either an infusion of sodium-GHB (390 mg x kg(-1) x 5 min(-1)) or the same volume of an equimolar solution of sodium chloride (6.9%). Plasma samples were taken for GHB assay (high-performance liquid chromatography) and the electroencephalography and blood pressure values were recorded. A two-compartment model with Michaelis-Menten elimination was fitted to the concentration-time data and a sigmoid E(max) model to the electroencephalographic effect effect site concentration curve allowing the study of the end organ sensitivity. Results Plasma concentration-time curves and the total volume of distribution in hypovolemic and normovolemic rats were comparable with only small but significant differences in central volume of distribution and the intercompartmental clearance. There was no significant difference either in the distribution from the plasma to the brain (k(e0)) or in the end organ sensitivity (EC50 = 335 +/- 76 microg/ml in control vs. 341 +/- 89 microg/ml in hypovolemic rats). GHB temporarily increased mean arterial pressure in both groups, which cannot be explained by the sodium salt alone. Conclusions Hypovolemia does not influence the overall concentration-time curve of GHB and induces no changes in the electroencephalographic effect of GHB in the rat. This difference with propofol may be due to the fact that it increases blood pressure but also due to its different pharmacokinetic properties.

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