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151. Comparison of intravenous and rectal aminophylline in the acutely ill asthmatic child
era1 of these. 0ne of the fractions was found to agglutinate type 0 red blood cells and the other fraction was shown to have hemolytic activity.
se for oral theophylline hr, M.D., K. Chang, ell, M.D., Denver, Cola.
M.D., and
ecause asthmatic patients are often treated with suboptimal T during the first 24 hr, we studied twelve asthmatic children to test the pharmacokinetic prediction that an optimal, near steady-state serum T level can be achieved very rapidiy by use of a loading dose (2X) equal to twice the maintenance dose (X) and in a dosing interval equal to t%. X equals the repeated dose giving T level of 10 to 20 pg/ml. This regimen was tested in a single-blind cross over study. After receiving X or 2X as an initial dose, subjects received X every 6 hr for 4 consecutive doses. Serum T levels (high-pressure liquid ‘chromatography) and spirometry values (Vanguard 500) were obtained at selected times after each dose.
Twenty-seven children were evaluated, 14 receiving the rectal preparation and 13 intravenous aminophylline. Seven received both rectal and intravenous drug for separate attacks. A maximum dose of 7 mg/kg was given. A nomogram was utilized to determine the dose. The therapeutic response was determined by multiple measurements of I-set forced expiratory volume (FEVi), vital capacity (VC), maximum midexpiratory flow rate (MMEFR), pulse, respiration, blood pressure, subjective score, and theopbylline serum levels over 2 to 6 hr. Peak serum levels for theophylline after moderately rapid (10 to 20 min) intravenous administration were reached in 30 min (mean, 27.9; range, 7.1 to 54 pg/ml) and decreased rapidly in 2 hr, frequently to less man 10 @g/ml. Serum theophylline levels via the rectal route reached peak values (mean, 12.8; range, 5.9 to 22.6 @g/ml) in 30 to 120 mm; a gradual decline followed. Favorable changes in FEVr, VC, and MMEFR correlate with serum levels of 10 to 20 hg/ml. It would appear that administration by rectum of a concentrated solution can be “safe” in recommended dosage (mg/kg). The current method of administration of intravenous aminophylline over 10 to 20 min should be reevaluated in the acutely ill patient.
152. The pharmacokinetics in pregnancy. P. L. Sutton,
of t
M.D., J. FL Koup, Pharm.D., J. Q. Rose, B.S., an E. Middleton, Jr., M.D., Buffalo, N.Y.
Preliminary analysis of the data from the first 9 subjects (Fig. 1) shows that optimal serum T levels can be rapidly achieved with a loading dose equal to 2X.
. Comparison of intravenous and recta! aminophylline in the acutely ill asthmatic Nell, M.D., Michael ~1. Greene, M.D.,
Schwartz,
In the past the rectal route for administration of aminopbylline earned well-deserved disfavor. In 1975, a new preparation for rectal use was introduced as a concentrated solution wbicb allowed precise dosage in mg/kg. This study compares me rectal solution with intravenous administration of aminophylline in children (6 to 16 yr) with acute asthma unresponsive to 2 subcutaneous doses of epinephrine.
The purpose of this study is to characterize the pharmacokinetics of theophylline during pregnancy. At present no data exists in the literature. Four observations were obtained in 3 women, ages 17 to 20 yr, between the fifth and eigbtb mo of gestation. Studies were performed in me fasting state, starting approximately 8 hr after the last medication, The patients were given their usual doses of oral theophylline, and serum samples were obtained at 0, 0.5, 1, 1.5, 2, 3, 4, 5, and 6 hr. Theophylline levels were assayed by highpressure liquid clwomatography The apparent volumes of distribution (Vr,) averaged 0.54 & 0.03 L/kg (21 SD; range, 0.51 to 0.56). Body clearances (CIB) averaged 0.046 ? 0.007 L/kg/hr. (?l SD; range, 0.36 to 0.052) and half-lives (t%) averaged 85 2 1.1 hr (? 1 SD; range, 7.5 to 9.9). When compared with literature values for adult female asthmatic patients Vr, and t% were increased significantly (p >O.Ol, p < 0.05, respectively). CIB, however, did not change (p < 0.1). To date we have studied 1 postpartum patient. Six weeks post partum her t% had decreased from 0.58 to 0.44 L/kg, but the CIB was unchanged (0.048 to 0.047 L/kg/hr). We are currently studying the other postpartum patients. Based on these data me daily dose of theophylline may have to be increased to accommodate me increase in patient weight. Since CIB remains unchanged> the dosage of theophylline on a mg/kg basis should remain unchanged.
se for oral theophylline hr, M.D., K. Chang, ell, M.D., Denver, Cola.
M.D., and
ecause asthmatic patients are often treated with suboptimal T during the first 24 hr, we studied twelve asthmatic children to test the pharmacokinetic prediction that an optimal, near steady-state serum T level can be achieved very rapidiy by use of a loading dose (2X) equal to twice the maintenance dose (X) and in a dosing interval equal to t%. X equals the repeated dose giving T level of 10 to 20 pg/ml. This regimen was tested in a single-blind cross over study. After receiving X or 2X as an initial dose, subjects received X every 6 hr for 4 consecutive doses. Serum T levels (high-pressure liquid ‘chromatography) and spirometry values (Vanguard 500) were obtained at selected times after each dose.
Twenty-seven children were evaluated, 14 receiving the rectal preparation and 13 intravenous aminophylline. Seven received both rectal and intravenous drug for separate attacks. A maximum dose of 7 mg/kg was given. A nomogram was utilized to determine the dose. The therapeutic response was determined by multiple measurements of I-set forced expiratory volume (FEVi), vital capacity (VC), maximum midexpiratory flow rate (MMEFR), pulse, respiration, blood pressure, subjective score, and theopbylline serum levels over 2 to 6 hr. Peak serum levels for theophylline after moderately rapid (10 to 20 min) intravenous administration were reached in 30 min (mean, 27.9; range, 7.1 to 54 pg/ml) and decreased rapidly in 2 hr, frequently to less man 10 @g/ml. Serum theophylline levels via the rectal route reached peak values (mean, 12.8; range, 5.9 to 22.6 @g/ml) in 30 to 120 mm; a gradual decline followed. Favorable changes in FEVr, VC, and MMEFR correlate with serum levels of 10 to 20 hg/ml. It would appear that administration by rectum of a concentrated solution can be “safe” in recommended dosage (mg/kg). The current method of administration of intravenous aminophylline over 10 to 20 min should be reevaluated in the acutely ill patient.
152. The pharmacokinetics in pregnancy. P. L. Sutton,
of t
M.D., J. FL Koup, Pharm.D., J. Q. Rose, B.S., an E. Middleton, Jr., M.D., Buffalo, N.Y.
Preliminary analysis of the data from the first 9 subjects (Fig. 1) shows that optimal serum T levels can be rapidly achieved with a loading dose equal to 2X.
. Comparison of intravenous and recta! aminophylline in the acutely ill asthmatic Nell, M.D., Michael ~1. Greene, M.D.,
Schwartz,
In the past the rectal route for administration of aminopbylline earned well-deserved disfavor. In 1975, a new preparation for rectal use was introduced as a concentrated solution wbicb allowed precise dosage in mg/kg. This study compares me rectal solution with intravenous administration of aminophylline in children (6 to 16 yr) with acute asthma unresponsive to 2 subcutaneous doses of epinephrine.
The purpose of this study is to characterize the pharmacokinetics of theophylline during pregnancy. At present no data exists in the literature. Four observations were obtained in 3 women, ages 17 to 20 yr, between the fifth and eigbtb mo of gestation. Studies were performed in me fasting state, starting approximately 8 hr after the last medication, The patients were given their usual doses of oral theophylline, and serum samples were obtained at 0, 0.5, 1, 1.5, 2, 3, 4, 5, and 6 hr. Theophylline levels were assayed by highpressure liquid clwomatography The apparent volumes of distribution (Vr,) averaged 0.54 & 0.03 L/kg (21 SD; range, 0.51 to 0.56). Body clearances (CIB) averaged 0.046 ? 0.007 L/kg/hr. (?l SD; range, 0.36 to 0.052) and half-lives (t%) averaged 85 2 1.1 hr (? 1 SD; range, 7.5 to 9.9). When compared with literature values for adult female asthmatic patients Vr, and t% were increased significantly (p >O.Ol, p < 0.05, respectively). CIB, however, did not change (p < 0.1). To date we have studied 1 postpartum patient. Six weeks post partum her t% had decreased from 0.58 to 0.44 L/kg, but the CIB was unchanged (0.048 to 0.047 L/kg/hr). We are currently studying the other postpartum patients. Based on these data me daily dose of theophylline may have to be increased to accommodate me increase in patient weight. Since CIB remains unchanged> the dosage of theophylline on a mg/kg basis should remain unchanged.