Comparison of pharmacokinetics between sarpogrelate hydrochloride immediate-release formulation and controlled-release formulation

Kim, Tae‐Eun; Kim, Jung-Ryul; Jung, Jin Ah; Kim, Suk-Ran; Lee, Jae Won; Jun, Hun; Lee, Soo-Youn; Huh, Wooseong; Ko, Ji Hyun

doi:10.5414/cp201777

Cited by 11 publications

(12 citation statements)

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“…The mean C max of M‐1 was 48.4 ± 9.82 ng/mL at T max (1 h; range, 0.33–1.5 h), and the AUC 0–∞ values were 86.5 ± 7.80 ng·h/mL. The pharmacokinetic parameters of sarpogrelate and M‐1 were similar to those reported in the literature .…”

Section: Resultssupporting

confidence: 78%

“…Several methods have been developed for the determination of sarpogrelate using LC–MS/MS in human and rat plasma . In clinical pharmacokinetic reports of sarpogrelate, an LC–MS/MS method for the separate determination of sarpogrelate and M‐1 in human plasma has been described . This method requires two different sample preparation processes and an especially time‐consuming and laborious SPE procedure for the determination of M‐1, which limits its bioanalytical throughput capacity.…”

Section: Introductionmentioning

confidence: 99%

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Simultaneous determination of sarpogrelate and its active metabolite in human plasma by liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study

Park

Bae

2014

J. Sep. Science

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We established a rapid and simple liquid chromatography with tandem mass spectrometry method for the simultaneous determination of sarpogrelate and its active metabolite, M-1, in human plasma. Sarpogrelate, M-1, and the internal standard, ketanserin, were extracted from a 50 μL aliquot of human plasma by protein precipitation using acetonitrile. Chromatographic separation was performed on a Shim-pack GIS ODS C18 column (100 × 3.0 mm; 3 μm) with an isocratic mobile phase consisting of 10 mM ammonium acetate and acetonitrile (70:30, v/v) at a flow rate of 0.6 mL/min; the total run time was <2.5 min. Mass spectrometric detection was conducted in selected reaction-monitoring mode with positive electrospray ionization at m/z 430.35 → 135.10 for sarpogrelate, m/z 330.30 → 58.10 for M-1, and m/z 395.70 → 188.85 for ketanserin. The linear ranges of concentration for sarpogrelate and M-1 were 1-1000 and 0.5-500 ng/mL, respectively. The coefficient of variation for the assay's precision was ≤9.95%, and the accuracy was 90.6-107%. All analytes were stable under various storage and handling conditions, and no relevant crosstalk and matrix effect was observed. This method was successfully applied to a pharmacokinetic study after oral administration of a 100 mg sarpogrelate tablet to healthy male Korean volunteers.

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Section: Resultssupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of sarpogrelate and its active metabolite in human plasma by liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study

Park

Bae

2014

J. Sep. Science

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“…In plasma protein-binding studies, the final concentrations of sarpogrelate or M-1 were both 0.5 and 10 mM. The LC-MS/MS conditions for determination of sarpogrelate and M-1 were optimized based on the conditions used in a previous study (Kim et al, 2013a).…”

Section: Methodsmentioning

confidence: 99%

“…After oral administration of 100 mg of sarpogrelate to healthy male subjects, sarpogrelate is rapidly absorbed from the gastrointestinal tract with a mean maximum plasma concentration (C max ) of 856.3 ng/mL at 0.7 hour and is rapidly eliminated from plasma with a half-life of 0.8 hour (Kim et al, 2013a). The active metabolite, M-1, reaches a C max of 49.3 ng/mL at 0.9 hour and exhibits slower elimination than sarpogrelate, with a half-life of 4.4 hours (Kim et al, 2013a). After absorption, sarpogrelate and M-1 further undergo glucuronide conjugations to form several metabolites, which are mainly excreted in bile (Kim et al, 2013b).…”

Section: Introductionmentioning

confidence: 99%

Selective Inhibition of Cytochrome P450 2D6 by Sarpogrelate and Its Active Metabolite, M-1, in Human Liver Microsomes

et al. 2013

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The present study was performed to evaluate the in vitro inhibitory potential of sarpogrelate and its active metabolite, M-1, on the activities of nine human cytochrome (CYP) isoforms. Using a cocktail assay, the effects of sarpogrelate on nine CYP isoforms and M-1 were measured by specific marker reactions in human liver microsomes. Sarpogrelate potently and selectively inhibited CYP2D6-mediated dextromethorphan O-demethylation with an IC 50 (K i ) value of 3.05 mM (1.24 mM), in a competitive manner. M-1 also markedly inhibited CYP2D6 activity; its inhibitory effect with an IC 50 (K i ) value of 0.201 mM (0.120 mM) was more potent than that of sarpogrelate, and was similarly potent as quinidine (K i , 0.129 mM), a well-known typical CYP2D6 inhibitor. In addition, sarpogrelate and M-1 strongly inhibited both CYP2D6-catalyzed bufuralol 19-hydroxylation and metoprolol a-hydroxylation activities. However, sarpogrelate and M-1 showed no apparent inhibition of the other following eight CYPs: CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2E1, or CYP3A4/5. Upon 30-minute preincubation of human liver microsomes with sarpogrelate or M-1 in the presence of NADPH, no obvious shift in IC 50 was observed in terms of inhibition of the nine CYP activities, suggesting that sarpogrelate and M-1 are not time-dependent inactivators. Sarpogrelate strongly inhibited the activity of CYP2D6 at clinically relevant concentrations in human liver microsomes. These observations suggest that sarpogrelate could have an effect on the metabolic clearance of drugs possessing CYP2D6-catalyzed metabolism as a major clearance pathway, thereby eliciting pharmacokinetic drug-drug interactions.

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“…For example, in our previous study, the coefficient of variation (CV) for the C max of sarpogrelate was determined to be approximately 50%. Similarly, other studies have shown that it is 35% . In addition, most of the PK parameters reported for sarpogrelate are not from healthy Chinese subjects .…”

mentioning

confidence: 84%

Bioequivalence of Sarpogrelate in Healthy Chinese Subjects Under Fasting and Fed Conditions: A 4‐Way Replicate Crossover Investigation by a Reference‐Scaled Average Bioequivalence Approach

Ding

Liu

Lou

et al. 2018

Clinical Pharm in Drug Dev

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Sarpogrelate is widely used to treat peripheral vascular disorders. However, it has been demonstrated to have a poor pharmacokinetic (PK) profile and marked within‐subject variability. Here, the bioequivalence of 2 formulations of sarpogrelate (100‐mg tablets) was assessed by using the reference‐scaled average bioequivalence (RSABE) method, and the PK parameters were quantified in healthy Chinese subjects under fasting (n = 38) and fed (n = 35) conditions. In this open and randomized 4‐way replicate study, a single dose of sarpogrelate was administered followed by a 3‐day washout period. The sarpogrelate concentration in blood samples was measured by liquid chromatography‐tandem mass spectrometry within 6 hours (fasting) or 10 hours (fed) of drug administration, and the PK parameters were determined by a noncompartmental model. The bioequivalence of the 2 formulations under both conditions was assessed using the ratios of ln(peak concentration [Cmax]) and ln(area under the concentration‐time curve [AUC]) within the limits based on the RSABE method. The 90% CIs for the ratios of lnCmax, lnAUC0‐t, and lnAUC0‐∞ were 0.8531–1.1100, 0.9616–1.0737, and 0.9550–1.0684, respectively, under fasting conditions and 0.8918–1.1076, 0.9818–1.0694, and 0.9818–1.0686, respectively, under fed conditions, which were within the RSABE acceptance limits. Food intake decreased the systemic exposure and the Cmax of sarpogrelate by 0.9‐fold and 0.5‐fold, respectively.

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Comparison of pharmacokinetics between sarpogrelate hydrochloride immediate-release formulation and controlled-release formulation

Abstract: After the administration of sarpogrelate hydrochloride CR and IR formulations using the same daily dose, AUCs were slightly higher for the CR formulation than for the IR formulation for both sarpogrelate and its metabolite M-1, but the C(max) values were similar.

Cited by 11 publications

References 0 publications

Simultaneous determination of sarpogrelate and its active metabolite in human plasma by liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study

Simultaneous determination of sarpogrelate and its active metabolite in human plasma by liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study

Selective Inhibition of Cytochrome P450 2D6 by Sarpogrelate and Its Active Metabolite, M-1, in Human Liver Microsomes

Bioequivalence of Sarpogrelate in Healthy Chinese Subjects Under Fasting and Fed Conditions: A 4‐Way Replicate Crossover Investigation by a Reference‐Scaled Average Bioequivalence Approach

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