Microdosing Assessment to Evaluate Pharmacokinetics and Drug Metabolism in Rats Using Liquid Chromatography-Tandem Mass Spectrometry

Ni, Jinsong; Ouyang, Hui; Aiello, Mauro; Seto, Carmai; Borbridge, Lisa; Sakuma, Takeo; Ellis, Robert; Welty, Devin; Acheampong, Andrew

doi:10.1007/s11095-008-9555-x

Cited by 42 publications

(25 citation statements)

References 18 publications

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“…The half-life of 1.86 hours in control group found in this study is similar to values reported by others for rats [30][31][32][33][34][35]. In the present study, the total body clearance of CBZ significantly decreased in 2 mg/kg rhGH treated rats compared to control rats and 0.1 mg/kg rhGH treated rats, by approximately 27% and 24%, respectively.…”

Section: Pharmacokinetics Of Carbamazepinesupporting

confidence: 91%

“…There are reported significant differences in drug clearance between male (0.96 L/hr/kg) and female (0.56 L/hr/kg), as well as between young (0.72 L/hr/kg) and old (0.32 L/hr/kg) rats [30,31]. The CBZ T 1/2 of 1.86 hours in the control group found in this study is comparable to values reported by others for rats [31][32][33][34][35].…”

Section: Pharmacokinetics Of Carbamazepinesupporting

confidence: 88%

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Effects of Short-Term Treatment with Recombinant Human Growth Hormone on Carbamazepine Pharmacokinetics in Rats

Lin

Lee²,

Ravis³

2013

Clin Exp Pharmacol

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Objectives: To investigate the pharmacokinetics of Carbamazepine (CBZ) in rats during growth hormone treatment.Methods: Recombinant Human Growth Hormone (rhGH) was injected subcutaneously at a daily dose of 0.1 mg/ kg, 2 mg/kg, or phosphate buffered saline (control) for 5 days in male Sprague-Dawley rats. On day 6, a dose of 25 mg/kg of CBZ was injected intravenously via a jugular vein cannula into the rat. Growth rate were compared between treatment groups. The pharmacokinetics of CBZ was determined from its concentrations in rats' blood and urinary samples.Results: Over the 5-day treatment period, growth rate were greater than control for the 2 mg/kg rhGH dosed group. The volume of distribution (V ss ) was significantly (p<0.05) decreased in the high dosed rhGH rats compared to the control group. Total body clearance (CL) in the 2 mg/kg rhGH group was also significantly (p<0.05) decreased compared with the control group (0.497 ± 0.076 L/hr/kg vs 0.685 ± 0.109 L/hr/kg). Urinary data showed that renal and metabolic clearances were both significantly (p<0.05) decreased in the 2 mg/kg rhGH group. Conclusions:A dose dependent effect of rhGH was observed on growth rates and CBZ pharmacokinetics in rats. After 5 days rhGH treatment, the volume of distribution of CBZ was significantly changed in the 2 mg/kg/day rhGH treated groups. In the 2 mg rhGH/kg treated rats, both renal and metabolic clearance of CBZ were also significantly decreased compared with the control group. Similar decreases in volume of distribution and both clearances may suggest the interaction may involve increased CBZ plasma protein binding during rhGH treatment in rats.

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Section: Pharmacokinetics Of Carbamazepinesupporting

confidence: 91%

Section: Pharmacokinetics Of Carbamazepinesupporting

confidence: 88%

Effects of Short-Term Treatment with Recombinant Human Growth Hormone on Carbamazepine Pharmacokinetics in Rats

Lin

Lee²,

Ravis³

2013

Clin Exp Pharmacol

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“…[7][8][9][10][11][12][13][14] However, the drug concentration of samples in a microdose study cannot be measured at an LLOQ of only ng/mL because of lack of sensitivity. 5,6,[15][16][17][18][19][20] In case of employing SPE or liquid-liquid extraction for sample preparation, it is possible to set the LLOQ at pg/mL, but total sample analysis is required, which demands increased time as the procedure of sample preparation is quite complex. 6,[15][16][17][18] If an online SPE method could be established to reduce the time required for sample preparation, Regular Article * To whom correspondence should be addressed.…”

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confidence: 99%

“…5,6,[15][16][17][18][19][20] In case of employing SPE or liquid-liquid extraction for sample preparation, it is possible to set the LLOQ at pg/mL, but total sample analysis is required, which demands increased time as the procedure of sample preparation is quite complex. 6,[15][16][17][18] If an online SPE method could be established to reduce the time required for sample preparation, Regular Article * To whom correspondence should be addressed. e-mail: yukari.tanaka@shionogi.co.jp the investment in system would increase.…”

mentioning

confidence: 99%

“…In addition, the obtained sensitivity might end up being lower than those reported previously, because of the smaller sample volume of non-clinical PK studies compared to clinical studies. 5,6,[15][16][17][18][19][20] Previously, we reported on a multiple injection method (MIM), which is a novel high-throughput analytical technique utilizing LC-MS/MS. 21) In the present study, fexofenadine was selected as a model compound, and we developed and validated the ultra high-sensitivity quantitative method of MIM for rat plasma samples without an internal standard (IS) compound by using simple sample treatment procedures like the protein precipitation method.…”

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confidence: 99%

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Development of a Highly Sensitive Methodology for Quantitative Determination of Fexofenadine in a Microdose Study by Multiple Injection Method Using Ultra-High Performance Liquid Chromatography with Tandem Mass Spectrometry

Tanaka

Yoshikawa

Yasui

2012

Biological & Pharmaceutical Bulletin

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An ultra high-sensitivity method for quantifying fexofenadine concentration in rat plasma samples by multiple injection method (MIM) was developed for a microdose study. In this study, MIM involved continuous injections of multiple samples containing the single compound into a column of the ultra-HPLC (UHPLC) system, and then, temporary trapping of the analyte at the column head. This was followed by elution of the compound from the column and detection by mass spectrometer. Fexofenadine, used as a model compound in this study, was extracted from the plasma samples by a protein precipitation method. Chromatographic separation was achieved on a reversed-phase C18 column by using a gradient method with 0.1% formic acid and 0.1% formic acid in acetonitrile as the mobile phase. The analyte was quantified in the positive-ion electrospray ionization mode using selected reaction monitoring. In this study, the analytical time per fexofenadine sample was approximately 2 min according to the UHPLC system. The method exhibited the linear dynamic ranges of 5-5000 pg/mL for fexofenadine in rat plasma. The intra-day precisions were from 3.2 to 8.7% and the accuracy range was 95.2-99.3%. The inter-day precisions and accuracies ranged from 3.5 to 8.4% and from 98.6 to 102.6%, respectively. The validated MIM was successfully applied to a microdose study in the rats that received oral administration of 100 µg/kg fexofenadine. We suggest that this method might be beneficial for the quantification of fexofenadine concentrations in a microdose clinical study.

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Agents Acting on Prostanoid and Thromboxane Receptors

Hall

Peace

Swarbrick

2010

Burger's Medicinal Chemistry and Drug Discovery

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Microdosing Assessment to Evaluate Pharmacokinetics and Drug Metabolism in Rats Using Liquid Chromatography-Tandem Mass Spectrometry

Abstract: This study has shown the promise of sensitive LC-MS/MS method to support microdose pharmacokinetics and drug metabolism studies in human.

Cited by 42 publications

References 18 publications

Effects of Short-Term Treatment with Recombinant Human Growth Hormone on Carbamazepine Pharmacokinetics in Rats

Effects of Short-Term Treatment with Recombinant Human Growth Hormone on Carbamazepine Pharmacokinetics in Rats

Development of a Highly Sensitive Methodology for Quantitative Determination of Fexofenadine in a Microdose Study by Multiple Injection Method Using Ultra-High Performance Liquid Chromatography with Tandem Mass Spectrometry

Agents Acting on Prostanoid and Thromboxane Receptors

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