Measurement of the class III antidysrhythmic drug, UK-68,798, in plasma by radioimmunoassay

Walker, Don K.; Aherne, G. Wynne; Arrowsmith, John; Cross, P. E.; Kaye, B.; Smith, Dennis A.; Stopher, D. A.; Wild, W.

doi:10.1016/0731-7085(91)80137-x

Cited by 28 publications

(12 citation statements)

References 4 publications

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“…Blood plasma samples were stored at −20°C and later analysed using radioimmunoassay techniques 17. The maximum plasma concentration, C max , and the area under the nine hour dofetilide plasma concentration v time curve, AUC 0–9 , were calculated for each subject.…”

Section: Methodsmentioning

confidence: 99%

Effects of intravenous dofetilide on induction of atrioventricular re-entrant tachycardia

Cobbe¹,

Campbell²,

Nathan³

et al. 2001

Heart

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Objective-To assess the eYcacy and safety of intravenous dofetilide in preventing induction of atrioventricular re-entrant tachycardia. Design-A multicentre, open, dose ranging trial. Fifty one patients with electrically inducible atrioventricular re-entrant tachycardia were allocated to one of five doses of dofetilide (1.5, 3, 6, 9, and 15 µg/kg), two thirds of the dofetilide dose being given over a 15 minute loading period and the remainder over a 45 minute maintenance period. Main outcome measure-Responders were defined as patients in whom dofetilide prevented reinduction of atrioventricular re-entrant tachycardia at the end of the infusion. Results-Intravenous dofetilide had no eVect on tachycardia inducibility at the two lower doses (1.5 and 3 µg/kg) but prevented the reinduction of tachycardia at the three higher doses (6, 9, and 15 µg/kg) at a rate of 36% (11/31). There was a clear relation between plasma dofetilide concentrations and eYcacy (p = 0.009). In non-responders, dofetilide increased the cycle length of induced atrioventricular re-entrant tachycardia. Dofetilide increased the atrial and ventricular eVective refractory periods, as well as the antegrade and retrograde eVective refractory period of the accessory pathway. Treatment related side eVects were reported in four patients, one with a new sustained incessant supraventricular tachycardia. Conclusions-Dofetilide shows promise as an agent for the prevention of atrioventricular re-entrant tachycardia in patients without structural heart disease. (Heart 2001;86:522-526)

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Section: Methodsmentioning

confidence: 99%

Effects of intravenous dofetilide on induction of atrioventricular re-entrant tachycardia

Cobbe¹,

Campbell²,

Nathan³

et al. 2001

Heart

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“…After a 10 Fg/kg oral dose of UK-68,798, the peak plasma concentration was 2.5 ng/ml at 3 h after receiving the drug, and the terminal elimination half-life was 0.081 h-' (34). Forty-eight hours after an intravenous or oral dose of UK-68,798 (10 pgkg), the plasma concentration was 0.05-0.12 ng/ml (34). In patients with coronary artery disease, UK-68,798 exhibited first-order kinetics with a mean clearance rate of 4.7 * 1.2 mliminikg, and a terminal elimination half-life of 9.7 h (0.103 h-') (28).…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…The oral bioavailability of UK-68,98 in the dog was determined to be between 72 and 100% (7). In human volunteers, after a 10 pgkg intravenous dose of UK-68,798, plasma levels of the drug declined in a biexponential manner with a termination half-life of 0.075 h-' (34). After a 10 Fg/kg oral dose of UK-68,798, the peak plasma concentration was 2.5 ng/ml at 3 h after receiving the drug, and the terminal elimination half-life was 0.081 h-' (34).…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…In human volunteers, after a 10 pgkg intravenous dose of UK-68,798, plasma levels of the drug declined in a biexponential manner with a termination half-life of 0.075 h-' (34). After a 10 Fg/kg oral dose of UK-68,798, the peak plasma concentration was 2.5 ng/ml at 3 h after receiving the drug, and the terminal elimination half-life was 0.081 h-' (34). Forty-eight hours after an intravenous or oral dose of UK-68,798 (10 pgkg), the plasma concentration was 0.05-0.12 ng/ml (34).…”

Section: Pharmacokineticsmentioning

confidence: 99%

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UK‐68,798, A Class III Antiarrhythmic Drug with Antifibrillatory Properties

Black

Lucchesi

1992

Cardiovascular Drug Reviews

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“…Several analytical methods for quantifying dofetilide (LCMS [24], HPLC [21,25] and RIA [26] or amlodipine (HPLC [9,[27][28][29][30][31], HPLC with radioactivity detection [32], HPLC with electrochemical detection [33], LCMS [34][35][36], GCMS [37] and GC with electron capture detection [38] in biological fluids have been reported. Unfortunately, all of these described methods do not allow the quantification of both drugs in the same run.…”

Section: Amlodipine Besylate (Norvascmentioning

confidence: 99%

Simultaneous Determination of Dofetilide and Amlodipine in Plasma by HPLC

Kaddar¹,

Pilote²,

Wong³

et al. 2013

J Chromat Separation Techniq

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Dofetilide is a Class III antiarrhythmic drug useful in the management of atrial fibrillation but also known to prolong the QT interval on the ECG and to induce malignant ventricular tachyarrhythmias such as torsades de pointes (TDP). Drugs with calcium channel-blocking properties contribute to decrease the incidence of TDP. Amlodipine is a dihydropyridine calcium channel antagonist. Considering the potentially safe and useful combined use of dofetilide and amlodipine, we undertook drug biotransformation studies. To perform studies aiming to evaluate the possible pharmacokinetic interaction between these drugs, a unique sensitive HPLC assay able to quantify both drugs simultaneously was required. A sensitive and specific HPLC method using a tandem of UV/fluorescence detection was described for the analysis of amlodipine and dofetilide in plasma. The within-day and between-day precision studies showed good reproducibility with coefficients of variation less than 10% for all the analytes. The limits of detection were 0.5 ng/mL and 0.25 ng/mL and the limit of quantification were 1.7 ng/mL and 0.8 ng/mL for dofetilide and amlodipine respectively. This new method could be of great value in many applications such as in vitro and in vivo pharmacokinetic and drug-drug interactions studies, as well as therapeutic drug monitoring.

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Measurement of the class III antidysrhythmic drug, UK-68,798, in plasma by radioimmunoassay

Cited by 28 publications

References 4 publications

Effects of intravenous dofetilide on induction of atrioventricular re-entrant tachycardia

Effects of intravenous dofetilide on induction of atrioventricular re-entrant tachycardia

UK‐68,798, A Class III Antiarrhythmic Drug with Antifibrillatory Properties

Simultaneous Determination of Dofetilide and Amlodipine in Plasma by HPLC

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