Population Pharmacokinetics of Olmesartan Following Oral Administration of its Prodrug, Olmesartan Medoxomil

Yoshihara, Kazutaka; Gao, Yuying; Shiga, Hiroshi; Wada, Daisuke; Hisaoka, Masafumi

doi:10.2165/00003088-200544120-00011

Cited by 29 publications

(27 citation statements)

References 18 publications

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“…In the previous population pharmacokinetic analysis of olmesartan after oral administration of its prodrug OM in healthy volunteers and hypertensive patients (Yoshihara et al, 2005), female sex was reported to be one of the effective covariates of a lower apparent oral clearance. However, the observed change was slight and thus not considerable (13.5% lower in women than men) to adjust the dosage.…”

Section: Discussionmentioning

confidence: 99%

Interindividual Variability of Carboxymethylenebutenolidase Homolog, a Novel Olmesartan Medoxomil Hydrolase, in the Human Liver and Intestine

et al. 2013

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Olmesartan medoxomil (OM) is a prodrug-type angiotensin II type 1 receptor antagonist. OM is rapidly converted into its active metabolite olmesartan by multiple hydrolases in humans, and we recently identified carboxymethylenebutenolidase homolog (CMBL) as one of the OM bioactivating hydrolases. In the present study, we further investigated the interindividual variability of mRNA and protein expression of CMBL and OM-hydrolase activity using 40 individual human liver and 30 intestinal specimens. In the intestinal samples, OM-hydrolase activity strongly correlated with the CMBL protein expression, clearly indicating that CMBL is a major contributor to the prodrug bioactivation in human intestine. The protein and activity were highly distributed in the proximal region (duodenum and jejunum) and decreased to the distal region of the intestine. Although there was high interindividual variability (16-fold) in both the protein and activity in the intestinal segments from the duodenum to colon, the interindividual variability in the duodenum and jejunum was relatively small (3.0-and 2.4-fold, respectively). In the liver samples, the interindividual variability in the protein and activity was 4.1-and 6.8-fold, respectively. No sex differences in the protein and activity were shown in the human liver or intestine. A genetically engineered Y155C mutant of CMBL, which was caused by a single nucleotide polymorphism rs35489000, showed significantly lower OM-hydrolase activity than the wild-type protein although no minor allele was genotyped in the 40 individual liver specimens.

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Section: Discussionmentioning

confidence: 99%

Interindividual Variability of Carboxymethylenebutenolidase Homolog, a Novel Olmesartan Medoxomil Hydrolase, in the Human Liver and Intestine

et al. 2013

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“…Minor differences were seen in the pharmacokinetics of olmesartan in Caucasian men and women, with females exhibiting an approximately 10-15% higher AUC and C max than males (Yoshihara et al, 2005), whereas no significant sex difference has been observed in Chinese subjects (Jiang et al, 2009). Although the C max values of olmesartan were similar in elderly compared with young adults, modest accumulation of olmesartan was observed in the elderly with repeated dosing (a 33% increase in AUC corresponding to a 30% reduction in renal clearance) (von Bergmann et al, 2001).…”

Section: E Age Sex and Ethnicitymentioning

confidence: 99%

“…The suspension formulation of olmesartan used in children is bioequivalent to the tablet formulation used in adults. Population pharmacokinetic analysis suggests that the pharmacokinetics of olmesartan do not differ between Western and Japanese populations (Yoshihara et al, 2005).…”

Section: E Age Sex and Ethnicitymentioning

confidence: 99%

“…After repeated dosing, the AUC was approximately tripled in patients with severe renal impairment (von Bergmann et al, 2001). On the basis of population pharmacokinetic analyses, the clearance of olmesartan is reduced by $30% in patients with severe renal impairment (Yoshihara et al, 2005). The pharmacokinetics of olmesartan in patients undergoing hemodialysis have been described (Tanaka et al, 2009) but not compared with those in subjects without renal impairment.…”

Section: F Renal and Hepatic Impairmentmentioning

confidence: 99%

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A Systematic Comparison of the Properties of Clinically Used Angiotensin II Type 1 Receptor Antagonists

et al. 2013

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“…It is a selective AT1 subtype angiotensin II receptor blocker (6,7), which was recently approved by the US-FDA (8) to treat patients with hypertension. This reduces blood pressure by causing vasodilation and reducing peripheral resistance (9). OLM is also reported to be effective in animal models of atherosclerosis, liver disorders and diabetic nephropathy (10).…”

mentioning

confidence: 99%

RP-HPLC-DAD method for determination of olmesartan medoxomil in bulk and tablets exposed to forced conditions

Sharma¹,

Pancholi²

2010

Acta Pharmaceutica

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Stability can be defined as the capacity of a drug substance or drug product to sustain its identity, strength, quality, and purity throughout the retest or expiration period (1). Stability testing of an active substance or finished product provides evidence of the quality of a drug substance or drug product to remain acceptable up to the stated period under storage conditions stated on the label. The International Conference on Harmonization (ICH) guidelines Q1A (R2) require the use of a validated stability-indicating assay method (SIAM) for stability testing of a drug substance or product (2). It also empha- A simple, sensitive and precise RP-HPLC-DAD method was developed and validated for the determination of olmesartan medoxomil (AT-II receptor blocker) in the presence of its degradation products. Olmesartan medoxomil and all the degradation products were resolved on a C 18 column with the mobile phase composed of methanol, acetonitrile and water (60:15:25, V/V/V, pH 3.5 by orthophosphoric acid) at 260 nm using a photodiode array detector. The method was linear over the concentration range of 1-18 mg mL -1 and precise with RSD < 1 % in intra-and inter-day study. Excellent recoveries of 99.3 ± 0.9 to 100.8 ± 1.2 % proved the accuracy of the method. Developed method was specific, as indicated by chromatographic resolution > 2.0 for each peak and sensitive with LOD 0.03 mg mL -1 and LOQ 0.1 mg mL -1 . The method was used to study the drug degradation behavior under forced conditions. Four degradation products (DP-I, II, III, IV) were formed during the degradation study in 0.1 mol L -1 HCl whereas only DP-I, II and III were formed in water, 0.01 mol L -1 NaOH and 3 % H 2 O 2 . No significant thermal or photolytic degradation was observed in solid drug. The method was applied successfully for the assay of olmesartan medoxomil in the tablet dosage form.

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Population Pharmacokinetics of Olmesartan Following Oral Administration of its Prodrug, Olmesartan Medoxomil

Cited by 29 publications

References 18 publications

Interindividual Variability of Carboxymethylenebutenolidase Homolog, a Novel Olmesartan Medoxomil Hydrolase, in the Human Liver and Intestine

Interindividual Variability of Carboxymethylenebutenolidase Homolog, a Novel Olmesartan Medoxomil Hydrolase, in the Human Liver and Intestine

A Systematic Comparison of the Properties of Clinically Used Angiotensin II Type 1 Receptor Antagonists

RP-HPLC-DAD method for determination of olmesartan medoxomil in bulk and tablets exposed to forced conditions

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