Determination of quinidine, dihydroquinidine, (3S)-3-hydroxyquinidine and quinidine N-oxide in plasma and urine by high-performance liquid chromatography

Nielsen, Flemming; Nielsen, Kristina Tomra; Brøsen, Kim

doi:10.1016/0378-4347(94)00259-2

Cited by 32 publications

(17 citation statements)

References 17 publications

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“…The volunteers had given their consent to participate on the basis of verbal and written information, and the protocol was approved by the regional Ethics Committee and the National Board of Health. Each volunteer took a single oral dose of 200 mg quinidine free base in gelatine capsule purified from dihydroquinidine [10], structural formula and purity was confirmed by NMR, mass spectroscopy and elemental analysis). Blood samples were obtained via a heparinised intravenous catheter (Venflon) and placed a heparinised Venoject tube at 0, 0.5 and 1 h, then hourly to 12 h and again at 14 and 16 h. Additional blood samples were 5O2 obtained at 24, 48, 72 and 96 h after drug administration.…”

Section: Subjectsmentioning

confidence: 99%

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Lack of relationship between quinidine pharmacokinetics and the sparteine oxidation polymorphism

Nielsen

Rosholm

Brøsen

1995

Eur J Clin Pharmacol

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Quinidine is a very potent inhibitor of CYP2D6, but the role of the enzyme in the biotransformation of quinidine has only been investigated in a single in vitro study and in two small in vivo experiments, with contradictory results. The present investigation was designed to present definite evaluation of whether quinidine is metabolised by CYP2D6. Eight poor metabolizers (PM) and 8 extensive metabolizers (EM) of sparteine each took one oral dose of 200 mg quinidine. In the EM, the total clearance, the clearance via 3-hydroxylation and the clearance via N-oxidation, were 33, 3.7 and 0.23 l.h-1, respectively. In the PM, the corresponding values were 29, 3.1 and 0.18 l.h-1, respectively. There were no statistically significant differences between EM and PM in any of these pharmacokinetic parameters. It is concluded that CYP2D6 is not an important enzyme for the oxidation of quinidine.

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Section: Subjectsmentioning

confidence: 99%

“…Quinidine, (3S)-3OH-quinidine and quinidine-N-oxide were assayed by a recently developed HPLC method, using fluorescence detection [10]. The level of quantitation was 10 nM in plasma and 25 n mol-1-1 in urine, for all three compounds.…”

Section: Quantitation Of Quinidine and Its Metabolitesmentioning

confidence: 99%

Lack of relationship between quinidine pharmacokinetics and the sparteine oxidation polymorphism

Nielsen

Rosholm

Brøsen

1995

Eur J Clin Pharmacol

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“…Quinidine, 3-hydroxyquinidine and quinidine-N-oxide in plasma and urine were analysed by HPLC methods described previously (Nielsen et al 1994). …”

Section: Methodsmentioning

confidence: 99%

Rifampicin Treatment Greatly Increases the Apparent Oral Clearance of Qninidine

Damkier

Hansen

Brøsen

1999

Pharmacology & Toxicology

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Abstract:We investigated the effect of cytochrome P450 induction by rifampicin on the in vivo oxidative metabolism of quinidine. The pharmacokinetics of a 200 mg oral single dose quinidine were studied before and after one week of daily treatment with 600 mg rifampicin in six healthy young male volunteers. Biomarker reactions of cytochrome P450 isozyme activities in the form of caffeine, sparteine, mephenytoin, tolbutamide and cortisol metabolism were applied. The median total apparent oral clearance and partial clearance by 3-hydroxylation of quinidine increased 9 times. The partial clearance by N-oxidation increased 6 times. The C,, and the elimination half life were reduced 3 times. No statistically significant changes were found for quinidine t , , , and renal clearance. The cortisol metabolic ratio increased 5 times, while no statistically significant effects were seen for other CYP marker reactions. The results indicate that the inductive effect of rifampicin is likely to be of clinical relevance particulary when used concomitantly with drugs metabolized by CYP3A4.Cytochome P4503A4 (CYP3A4) accounts for approximately 30% of the total human liver cytochrome content and contributes to the oxidative metabolism of a wide range of drugs. The activity of CYP3A4 varies at least 10 times among individuals (Shimada et al. 1994), and the search for a suitable biomarker reaction of CYP3A4 activity, in order to assess CYP3A4 activity on an individual basis, is intense.

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“…This method utilizes isocraticmode with UV detection, which is more feasible and less time-consuming than any other method of detection. Although a number of methods are available for quantification of quinidine in various biological matrices [14][15][16], the uniqueness of the present method is its ability to simultaneously quantify passive integrity markers. The proposed method was further used to elucidate the pH-dependent functional activity of P-gp in limiting intestinal absorption of quinidine.…”

Section: Introductionmentioning

confidence: 99%

pH-dependent functional activity of P-glycoprotein in limiting intestinal absorption of protic drugs

Varma

Sarkar

Kapoor

et al. 2005

Journal of Chromatography B

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Determination of quinidine, dihydroquinidine, (3S)-3-hydroxyquinidine and quinidine N-oxide in plasma and urine by high-performance liquid chromatography

Cited by 32 publications

References 17 publications

Lack of relationship between quinidine pharmacokinetics and the sparteine oxidation polymorphism

Lack of relationship between quinidine pharmacokinetics and the sparteine oxidation polymorphism

Rifampicin Treatment Greatly Increases the Apparent Oral Clearance of Qninidine

pH-dependent functional activity of P-glycoprotein in limiting intestinal absorption of protic drugs

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