Quantitative determination of atorvastatin and ortho-hydroxy
atorvastatin in human plasma by liquid chromatography tandem mass
spectrometry and pharmacokinetic evaluation

Bx, He; Shi, Lei; Qiu, Jiamin; Zeng, Xianlu; Tao, Ling; R, Li; Chen, Hong; Xl, Gu; Fy, Dong; Yang, Longbao; Sj, Zhao

doi:10.1358/mf.2010.32.7.1487086

Cited by 7 publications

(4 citation statements)

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“…A simple protein precipitation was applied to extract metformin from the plasma. Validated LC-MS/MS methods were used to measure the study drugs 21,22. The assay had lower limits of quantification (LLQ) in plasma, 0.2 ng/mL for atorvastatin and 2-OH-atorvastatin, and 10 ng/mL for metformin.…”

Section: Methodsmentioning

confidence: 99%

<p>Pharmacokinetics of fixed-dose combination of atorvastatin and metformin compared with individual tablets</p>

Ghim

Phương

Kim

et al. 2019

DDDT

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Purpose: The aims of this study was to investigate the mutual pharmacokinetic interactions between steady-state atorvastatin and metformin and the effect of food on the fixed-dose combined (FDC) tablet of atorvastatin and metformin extended release (XR). Subjects and methods: Study 1, an open-labeled, fixed sequence, multiple-dose pharmacokinetic drug-drug interaction study, was divided into 2 parts. Atorvastatin (40 mg) or metformin (1,000 mg) XR tablets were administered once daily via mono- or co-therapy for 7 days. Plasma levels of atorvastatin and 2-OH-atorvastatin, were quantitatively determined for 36 h in part A (n=50) while metformin plasma concentration was measured up to 24 h in part B (n=16) after the last dosing. Study 2, a randomized, open-labeled, single-dose, two-treatment, two-period, two-sequence crossover study, involved 27 healthy subjects to investigate the impact of food intake on the pharmacokinetics of a combined atorvastatin/metformin XR 20/500 mg (CJ-30056 20/500 mg) tablet. Results: After multiple doses of mono- or co-therapy of atorvastatin (40 mg) and metformin (1,000 mg) XR, the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) for the peak plasma concentration at steady state (C max,ss ) and area under the plasma concentration–time curve during the dosing interval at steady state (AUC τ,ss ) were 1.07 (0.94–1.22) and 1.05 (0.99–1.10) for atorvastatin, 1.06 (0.96–1.16) and 1.16 (1.10–1.21) for 2-OH-atorvastatin, and 1.00 (0.86–1.18) and 0.99 (0.87–1.13) for metformin, respectively. Food delayed time to reach maximum concentration (t max ), decreased atorvastatin C max by 32% with a GMR (90% CI) of 0.68 (0.59–0.78), and increased metformin AUC t by 56% with a GMR (90% CI) of 1.56 (1.43–1.69). Conclusion: No clinically relevant pharmacokinetic interaction was seen when atorvastatin was co-administered with metformin. Food appeared to change the absorption of atorvastatin and metformin from an FDC formulation. These alterations were in accordance with those described with the single reference drugs when ingested with food.

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Section: Methodsmentioning

confidence: 99%

<p>Pharmacokinetics of fixed-dose combination of atorvastatin and metformin compared with individual tablets</p>

Ghim

Phương

Kim

et al. 2019

DDDT

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“…Analyte was detected by validated LC-MS/MS methods. [14,15] The lower limit of quantification (LLQ) for the plasma assay was 0.2 ng/mL for atorvastatin and 2-OH atorvastatin and 10 ng/mL for metformin. The linear calibration range was 0.2-100 ng/mL for atorvastatin and 2-OH atorvastatin and 10-3,000 ng/mL for metformin.…”

Section: Blood Sample Collection and Bioanalysismentioning

confidence: 99%

Pharmacokinetics of atorvastatin and sustained-release metformin fixed-dose combination tablets: two randomized, open-label, 2-way crossover studies in healthy male subjects under fed conditions

Choi

Park

Kim

et al. 2017

Transl Clin Pharmacol

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Two separate studies were conducted to establish bioequivalence (BE) for two doses of atorvastatin/ metformin sustained-release (SR) fixed dose combination (FDC) versus the same dosage of the individual component (IC) tablets in healthy male subjects under fed conditions (study 1, BE of atorvastatin/metformin SR 20/500 mg FDC; study 2, BE of atorvastatin/metformin SR 20/750 mg FDC). Each study was a randomized, open-label, single oral dose, two-way crossover design. Serial blood samples were collected pre-dose and up to 36 hours post-dose for atorvastatin and 24 hours for metformin. Plasma concentrations of atorvastatin, 2-OH atorvastatin and metformin were analyzed using a validated liquid chromatography tandem mass-spectrometry. A non-compartmental analysis was used to calculate pharmacokinetic (PK) variables and analysis of variance was performed on the lognormal-transformed PK variables. A total of 75 subjects completed the study 1 (36 subjects) and study 2 (39 subjects). The 90% confidence intervals for the adjusted geometric mean ratio of Cmax and the AUC0-t were within the predefined 0.80 to 1.25 range. The number of subjects reporting at least one adverse event following FDC treatments was comparable to that following IC treatments. The two treatments were well tolerated. Therefore, atorvastatin/metformin SR 20/500 mg and 20/750 mg FDC tablets are expected to be used as alternatives to IC tablets to decrease the pill burden and increase patient compliance.

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“…For clopidogrel, we used a fast, sensitive and specific LC-MS/MS bioanalytical method validated for determination of unchanged clopidogrel in human plasma. 22 …”

Section: Pharmacokineticsmentioning

confidence: 99%

Endothelial Progenitor Cell Mobilization and Platelet Microparticle Release Are Influenced by Clopidogrel Plasma Levels in Stable Coronary Artery Disease

França

Pinheiro

Izar

et al. 2012

Circ J

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Quantitative determination of atorvastatin and ortho-hydroxy atorvastatin in human plasma by liquid chromatography tandem mass spectrometry and pharmacokinetic evaluation

Cited by 7 publications

References 0 publications

<p>Pharmacokinetics of fixed-dose combination of atorvastatin and metformin compared with individual tablets</p>

<p>Pharmacokinetics of fixed-dose combination of atorvastatin and metformin compared with individual tablets</p>

Pharmacokinetics of atorvastatin and sustained-release metformin fixed-dose combination tablets: two randomized, open-label, 2-way crossover studies in healthy male subjects under fed conditions

Endothelial Progenitor Cell Mobilization and Platelet Microparticle Release Are Influenced by Clopidogrel Plasma Levels in Stable Coronary Artery Disease

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