RESUMEN
The clinical pharmacology of human recombinant erythropoietin (epoetin) was studied in order to compare the effectiveness of various routes and dosing schedules in dialysis patients. Thirty-six patients received epoetin beta three times a week i.v. for at least 12 wk. The mean dose needed to achieve target hemoglobin was 225 +/- 36 U/kg per week (median dose, 180 U/kg per week). Twenty-eight of 36 patients who were converted to a once-a-week i.v. schedule increased their requirements to 429 +/- 50 U/kg per week in order to maintain a target hematocrit of 33 to 40 vol%. Twelve of 28 patients could maintain their target hematocrit when dosed once a week s.c. at 84 +/- 10 U/kg. The other 16 patients required 137 +/- 15 U/kg per week divided into two doses. In the entire group of 28 patients, the weekly requirement for epoetin was reduced by 50% when the s.c. route was used two or three times a week. Pharmacokinetic studies performed during chronic therapy indicated rapid clearance of erythropoietin (t1/2 of 6.8 +/- 0.3 h). Single i.v. doses greater than 150 U/kg were required to increase basal erythropoietin by 30 mU/mL at 44 h postdosing. With s.c. dosing, such increments in erythropoietin levels frequently persisted beyond 60 h because of prolonged and slow absorption. Pharmacokinetic simulations in conjunction with clinical correlation of the erythropoietic response suggest that the duration that the erythropoietin levels are maintained, and not the absolute peaks, is the primary determinant of efficacy. This may result from nonlinearity in the dose response. Pharmacokinetic simulation also indicated that i.v. dosing could not maintain adequate interdialytic erythropoietin levels, whereas s.c. dosing could. Cost analysis indicated that the use of s.c. dosing two or three times a week at an average total weekly dose of 110 to 120 U/kg is effective treatment of anemia in most dialysis patients.
Asunto(s)
Anemia/terapia , Eritropoyetina/uso terapéutico , Factores Inmunológicos/uso terapéutico , Adolescente , Adulto , Anciano , Anemia/economía , Anemia/etiología , Esquema de Medicación , Eritropoyesis/efectos de los fármacos , Eritropoyetina/administración & dosificación , Eritropoyetina/farmacocinética , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/farmacocinética , Inyecciones Intravenosas , Inyecciones Subcutáneas , Hierro/sangre , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/uso terapéutico , Diálisis RenalRESUMEN
Calcium antagonists are now recommended as monotherapy for the treatment of mild to moderate essential hypertension by the Joint National Committee (JNC) on the Detection, Evaluation, and Treatment of High Blood Pressure. Based on a statement in the 1988 JNC report that black and elderly patients tend to respond better to calcium antagonists, we reviewed the literature to examine the predictive value of age and race to the antihypertensive response of calcium antagonists. The majority of studies we reviewed failed to substantiate the JNC statement and well-promulgated reports in the literature suggesting preferential action of calcium antagonists in the elderly, or their superiority when compared with diuretics, beta-adrenergic blockers, and angiotensin-converting enzyme inhibitors. Although not noted by the JNC, pretreatment blood pressure appeared to be an important predictor of the antihypertensive response to calcium antagonists. The literature reviewed indicates that calcium antagonists have comparable efficacy in black and white hypertensive patients. However, the limited comparative studies reviewed support the JNC statement that, as with diuretics, blacks have a greater antihypertensive response with calcium antagonists than with beta-adrenergic blockers or angiotensin-converting enzyme inhibitors.
Asunto(s)
Antihipertensivos/uso terapéutico , Población Negra , Bloqueadores de los Canales de Calcio/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertensión/etnología , Antagonistas Adrenérgicos beta/uso terapéutico , Factores de Edad , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Diuréticos/uso terapéutico , HumanosRESUMEN
The effects of labetalol, diltiazem and verapamil on antipyrine and indocyanine green clearance were evaluated in a placebo-controlled, repeated measures evaluation. Twelve healthy subjects received either labetalol (200 mg every 12 hours), diltiazem (90 mg. every 8 hours), verapamil (80 mg every 8 hours), or placebo (every 12 hours) for 4 days. On the morning of Day 3 immediately following their dose, the subjects assumed the supine position for 90 minutes, after which time a 0.5 mg/kg dose of indocyanine green was administered. Blood samples were obtained serially over a 20 minutes period for indocyanine green plasma concentration determinations by HPLC. Ten minutes later, subjects ingested a 1.2 Gm. dose of antipyrine and blood samples were obtained over a 48 hour period for antipyrine plasma concentration determinations by HPLC. A 2 week washout period separated treatment sequences. Mean (SD) antipyrine clearance (L/hr/kg) following diltiazem [0.028 (0.010)] and verapamil [0.030 (0.012)] treatment was significantly lower than that observed following placebo [0.039 (0.012)]. Antipyrine clearance following labetalol administration [0.033 (0.010)] was not significantly different from that observed following placebo, diltiazem or verapamil administration. No effects of these drugs on indocyanine green clearance could be detected.
Asunto(s)
Antipirina/metabolismo , Diltiazem/farmacología , Verde de Indocianina/metabolismo , Labetalol/farmacología , Verapamilo/farmacología , Adulto , Semivida , Humanos , Masculino , Distribución AleatoriaRESUMEN
Antipyrine is a pyrazole derivative used extensively as a marker for hepatic drug metabolizing enzyme activity. A subject participating in a clinical trial employing antipyrine experienced an acute allergic reaction to the drug which was characterized by diaphoresis, flushing, swelling of the throat, difficulty in breathing, vomiting, swelling of the upper lip, and a diffuse urticarial rash. Intravenous administration of diphenhydramine markedly improved the symptomatology. Clinical investigators as well as study participants should be alerted to the potential for antipyrine to cause an acute allergic reaction.
Asunto(s)
Antipirina/efectos adversos , Hipersensibilidad a las Drogas/etiología , Enfermedad Aguda , Adulto , Humanos , Hígado/enzimología , MasculinoRESUMEN
The antihypertensive effects of the 5-HT2 receptor antagonist ketanserin were evaluated in 16 patients with uncomplicated essential hypertension. Following a three week single-blind placebo treatment period, patients were randomized to receive in a double-blind manner oral ketanserin 20 mg or 40 mg twice a day for 10 weeks. In the racially mixed patient population, mean (+/- SD) seated blood pressure 12 hours after the last dose of placebo was 161 +/- 11/99 +/- 9 mm Hg and 155 +/- 19/98 +/- 10 mm Hg after ketanserin (P greater than .05). Ketanserin 20 mg twice a day did not lower blood pressure significantly. In contrast, 40 mg twice a day significantly decreased systolic blood pressure (P less than .02), and lowered diastolic blood pressure (P = .06). White patients (N = 7) showed a significant decrease in blood pressure (BP) with ketanserin treatment (158 +/- 5/98 +/- 8 vs. 147 +/- 13/92 +/- 6 mm Hg, P less than .05) while black patients (N = 9) did not (165 +/- 13/100 +/- 9 vs. 161 +/- 21/102 +/- 10 mm Hg, P greater than .05). For black patients only, significant correlations were observed between body weight and the change in diastolic BP (r = -.86, P less than .005). The racial difference in response to ketanserin could not be attributed to differences between the two groups in age, sex, body weight, pretreatment blood pressure or ketanserin dose. The nature of the racial difference in the chronic antihypertensive response to ketanserin warrants further evaluation.
Asunto(s)
Peso Corporal , Hipertensión/tratamiento farmacológico , Ketanserina/uso terapéutico , Adulto , Anciano , Aldosterona/sangre , Aldosterona/orina , Población Negra , Presión Sanguínea/efectos de los fármacos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Renina/sangre , Población BlancaRESUMEN
A 41-year-old man with combined renal and hepatic dysfunction was noted to have marked elevations in serum digoxin concentration subsequent to the discontinuation of digoxin therapy. These elevations (peak value 8.6 ng/ml), as measured by both radioimmunoassay and fluorescence polarization immunoassay, were not associated with electrocardiographic evidence of digitalis toxicity. Using a combined high-performance liquid chromatography/radioimmunoassay, accumulation and immunoassay cross-reactivity of conjugates of digoxigenin monodigitoxoside (cardioinactive metabolites of digoxin) were found to be the basis of the observed false elevation in digoxin concentration.