ABSTRACT
The effect of dofetilide on the steady-state pharmacokinetics of digoxin was evaluated in a randomized, double-blind study. Five days of dofetilide treatment did not significantly affect steady-state pharmacokinetic variables of digoxin compared with placebo; therefore, the use of dofetilide does not necessitate an adjustment in digoxin dose to maintain therapeutic digoxin levels.
Subject(s)
Anti-Arrhythmia Agents/pharmacology , Digoxin/pharmacokinetics , Phenethylamines/pharmacology , Sulfonamides/pharmacology , Adult , Anti-Arrhythmia Agents/blood , Anti-Arrhythmia Agents/pharmacokinetics , Digoxin/blood , Digoxin/pharmacology , Double-Blind Method , Drug Interactions , Humans , Male , Phenethylamines/blood , Sulfonamides/bloodABSTRACT
The class III antiarrhythmic drug dofetilide is known to prolong action potential duration by specific blockade of the delayed rectifier potassium channel Ik. As dofetilide is likely to be used in the treatment of atrial arrhythmias it is important to determine the relative sensitivity of the atrium and ventricle in man. Twelve male patients underwent monophasic action potential and refractory period recordings from the high right atrium and right ventricular septum. The patients received either 8 micrograms.kg-1 dofetilide or placebo intravenously. The mean QTc was prolonged by 11% (SD 5%, P < 0.00001) in the active group; the mean monophasic action potential increased by 31% (SD 15%, P < 0.0005) in the atrium and 27% (SD 9%, P < 0.00005) in the ventricle; the mean effective refractory period increased by 30% (SD 16%, P < 0.0005) in the atrium and 20% (SD 6%, P < 0.0001) in the ventricle. No significant change occurred in the placebo group. There was no significant difference in effect between the two chambers. The change in QTc did not accurately reflect acute changes in refractory period or monophasic action potential duration. This has important implications for the use of QT prolongation to assess the acute effect of class III drugs.
Subject(s)
Angina Pectoris/drug therapy , Angina Pectoris/physiopathology , Anti-Arrhythmia Agents/therapeutic use , Atrial Function/drug effects , Phenethylamines/therapeutic use , Sulfonamides/therapeutic use , Ventricular Function/drug effects , Action Potentials/drug effects , Cardiac Pacing, Artificial , Double-Blind Method , Electrocardiography , Humans , Male , Middle Aged , Reaction Time/drug effects , Refractory Period, ElectrophysiologicalABSTRACT
A combined series of 101 twin pregnancies for whom routine hospital rest during the last trimester was replaced by intensified antenatal care in a special twins clinic was studied. Perinatal mortality and morbidity was similar to that found in a comparison group of 137 twin pregnancies under the care of consultants and not referred to the twins clinic. Routine cervical assessments and uterine activity measurements were unhelpful in predicting premature delivery. Urinary oestrogens and ultrasonic measurements of fetal biparietal diameter were of little or no value in predicting weight for gestational age but the ultrasonic measurement of abdominal circumference provided limited information on fetal growth. The contribution of a placebo effect to the results of patients receiving more personalised care cannot be discounted.
Subject(s)
Pregnancy, Multiple , Prenatal Care , Adolescent , Adult , Bed Rest , Cephalometry , Cervix Uteri/physiopathology , Female , Fetus , Humans , Infant Mortality , Infant, Newborn , Obstetric Labor, Premature/diagnosis , Pregnancy , Twins , UltrasonographyABSTRACT
In a double blind trial, 25 patients with twin pregnancy were given 40 mg of ritodrine hydrochloride by mouth daily and 24 similar patients received a placebo. The ritodrine group had no significant prolongation of pregnancy nor increase in birth weight, and a high incidence of side effects occurred.
Subject(s)
Obstetric Labor, Premature/prevention & control , Pregnancy, Multiple , Propanolamines/therapeutic use , Ritodrine/therapeutic use , Clinical Trials as Topic , Double-Blind Method , Female , Fetal Growth Retardation/prevention & control , Humans , Infant, Newborn , Placebos , Pregnancy , Ritodrine/adverse effects , TwinsSubject(s)
Obstetrics , Anesthesia, Epidural , Anesthesia, Obstetrical , Female , Humans , Labor, Obstetric , Obstetric Labor, Premature , Placenta Diseases , Placental Insufficiency , Pregnancy , Pregnancy Trimester, First , Pregnancy Trimester, Second , Pregnancy Trimester, Third , Rh-Hr Blood-Group SystemABSTRACT
Total plasma cortisol, the 'cortisol resin uptake ratio' (cortisol RUR), and 'free cortisol index' (FCI) were estimated in 23 pregnant women from 12 weeks to term and at six weeks post partum. Total plasma cortisol rose continually throughout pregnancy; the cortisol RUR rose up to 20 to 23 weeks and then fell slowly and the FCI also rose although more slowly than the total cortisol. All parameters fell to non-pregnant levels at six weeks post partum. It is confirmed that a true rise in metabolically active cortisol occurs during pregnancy.
