The influence of chronic verapamil treatment on antipyrine elimination was studied in eight angina patients. Antipyrine half-life (mean ± s.d.) was 13.1 ± 1.15 h at the start of therapy and 16.6 ± 3.05 h (P < 0.05) during chronic oral administration of verapamil (80 -120 mg four or three times daily for 4 to 7 months). There was a significant decrease in antipyrine clearance (mean ± s.d, 43.2 ± 16.8 ml min-' vs 28.7 ± 16.6 ml min-', P < 0.01) while the change of distribution volume was insignificant. Verapamil elimination was also found to be impaired after chronic dosing as compared to single administration. Half-lives measured from the concentration vs time and urinary excretion rate vs time curves were both prolonged and oral clearance was decreased. Our results suggest that the inhibition of drug-metabolizing enzymes accounts for the impairment of verapamil elimination on chronic administration.
1 The possibility of development of tolerance to the anti-ischaemic and anti-anginal effects of nifedipine during sustained administration for 2 months was studied in 15 patients with stable angina pectoris by means of repeated exercise tests on a treadmill. 2 After acute administration of nifedipine (20-30 mg) substantial anti-ischaemic and anti-anginal effects lasted for at least 4 h in all patients. 3 During sustained nifedipine treatment with a dose schedule which provided continuous anti-ischaemic effect during a day (mean daily dose 82.7 ± 6.0 mg, range 60-120 mg) a substantial attenuation of this effect was registered. The duration of the anti-ischaemic effect was 5.4 ± 0.3 h after acute administration, decreasing significantly to 3.6 ± 0.4 h during sustained administration. 4 The attenuation of the nifedipine effect was not associated with worsening of the patients' condition. 5 Plasma concentrations of nifedipine and its metabolite were similar after acute administration and during sustained treatment. Protein binding of nifedipine also remained constant during the study. 6 There was marked interindividual variation in the degree of attenuation of the nifedipine effect during sustained administration. In five patients nearly complete loss of nifedipine efficacy was registered. Eight to ten days after stopping regular administration of nifedipine only partial restoration of nifedipine effect was observed. 7 We conclude that during sustained nifedipine administration tolerance to its antiischaemic, anti-anginal and circulatory effects develops in a substantial number of patients with stable angina pectoris.
Serum free fractions of nifedipine, verapamil and some of their metabolites were measured in patients with ischaemic heart disease receiving single oral dose and chronic monotherapy and were compared with those obtained in vitro. The percentages of unbound nifedipine and verapamil in vitro (concentration range 50‐200 and 150‐400 ng ml‐1, respectively) were 2.51 and 7.23%, respectively, and did not differ from those found on monotherapy with these drugs (2.05 and 8.08%, respectively), and after single dosing. It is suggested that, during treatment with nifedipine or verapamil, their serum metabolites do not affect binding of the parent drugs to serum proteins.
Кафедра терапии и семейной медицины факультета усовершенствования врачей Российского государственного медицинского университета. 125047, Москва, 2-й Тверской-Ямской пер., д.10 (Клиника OAO "Медицина") Влияние острой физической нагрузки различной интенсивности на состояние липидного обмена у мужчин среднего возраста Г.Е. Ройтберг, И.Д. Сластникова, О.Ю. Дмитриева*, Т.И. Ушакова Кафедра терапии и семейной медицины факультета усовершенствования врачей Российского государственного медицинского университета. 125047, Москва, 2-й Тверской-Ямской пер., д.10 (Клиника OAO "Медицина") Цель. Изучить влияние острой физической нагрузки различной интенсивности на показатели липидного обмена у мужчин среднего возраста. Материал и методы. Клинически здоровым мужчинам (n=54) в возрасте 30-45 лет без ожирения были проведены две пробы с физической нагрузкой средней и высокой интенсивности с последующей оценкой состояния липидного профиля (уровней общего холестерина, холестерина липопротеидов высокой плотности, триглицеридов и коэффициента атерогенности). Влияние физической нагрузки на липидный спектр изучалось как в целой группе, так и у пациентов с инсулинорезистентностью и без нее. Результаты. Острая физическая нагрузка умеренной и высокой интенсивности оказывала благоприятный эффект на показатели липидного обмена (способствует повышению уровня холестерина липопротеидов высокой плотности и снижению коэффициента атерогенности). С увеличением интенсивности физической нагрузки происходило дальнейшее нарастание благоприятных сдвигов липидного обмена у пациентов без инсулинорезистентности. У пациентов с инсулинорезистентностью ответ на нагрузку был выражен слабее, а увеличение интенсивности нагрузки не приводило к значимым благоприятным изменениям липидного профиля. Заключение. При разработке профилактических программ для коррекции факторов риска сахарного диабета 2 типа и сердечно-сосудистых заболеваний следует учитывать, что реакция на физическую нагрузку может зависеть от особенностей исходного метаболизма. Ключевые слова: острая физическая нагрузка, интенсивность физической нагрузки, инсулинорезистентность, липидный обмен.
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