Determination of indomethacin in serum and urine by electron-capture gas-liquid chromatography

Helleberg, Lars

doi:10.1016/s0021-9673(00)81078-x

Cited by 49 publications

(8 citation statements)

References 8 publications

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“…The plasma was separated in a centrifuge and stored at -20 °C. The assay of plasma indometh acin level was carried out by the electron capture gas chromatographic method [7] at Merck, Sharpe & Dohme research laboratory.…”

Section: Pharmacokinetic Studymentioning

confidence: 99%

Indomethacin Therapy in Premature Infants with Patent Ductus Arteriosus - Determination of Therapeutic Plasma Levels

et al. 1989

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To determine the therapeutic range of plasma indomethacin levels for ductus closure, we evaluated the ductus response and renal side effects on two therapeutic regimens using different dosage; regimen I received 0.3 mg/kg q 24 h for a maximum of 3 doses, and regimen II received 0.1, 0.2 and 0.3 mg/kg at 24-hour intervals, for a maximum of 3 doses if needed. Infants in regimen I had significantly higher plasma indomethacin and higher ductus response rate than infants in regimen II. Urine output (U/O) was comparable between the regimens, but serum sodium was lower in regimen I than in regimen II. In both regimens, U/O and serum sodium returned to normal by 72 h. The plasma indomethacin levels at 12 h after 1 dose correlated significantly with ductus response and hyponatremia. There appeared to be a minimal level of plasma indomethacin above which U/O decreased; with a plasma level > 170 ng/ml the majority (>97%) of infants showed a decrease in U/O. While there was a 50% or greater chance that ductus would close when the plasma levels reached 600 ng/ml or more, a great proportion of infants would also develop renal side effects. Thus, a safe therapeutic range of plasma indomethacin appeared to be very narrow. However, when the dose of indomethacin is increased to optimize constrictive response, there is no significant increase in incidence and severity of renal adverse effects. In view of the transient nature of renal side effects, they should not hinder indomethacin therapy if ductus closure is indicated.

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Section: Pharmacokinetic Studymentioning

confidence: 99%

Indomethacin Therapy in Premature Infants with Patent Ductus Arteriosus - Determination of Therapeutic Plasma Levels

et al. 1989

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“…Blood samples were kept at 4°C for 1 night before separation of plasma by centrifugation. Plasma samples were stored at -20°C until measurement of indomethacin by gas-liquid chromatography (12). In some studies, sagittal cross sections of the heart and great vessels were photographed as reported previously (7).…”

Section: Methodsmentioning

confidence: 99%

Increased Constriction of the Ductus Arteriosus with Combined Administration of Indomethacin and Betamethasone in Fetal Rats

Momma

Takao

1989

Pediatr Res

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ABSTRACT. To find a better treatment for patent ductus arteriosus of preterm infants, we studied the combined effect of indomethacin and betamethasone on the fetal ductus in rats. We used a rapid whole-body freezing technique, and the ratio of the inner diameter of the ductus to the main pulmonary artery, which was 1.0 in controls, was used as an index of constriction. Indices of ductal constriction 4 h after administration of indomethacin (1 mg/kg) alone, betamethasone (1 mg/kg) alone or in combination in near-term rats were 0.56 f 0.05 (mean f SEM), 0.76 f 0.06, and 0.17 f 0.03, respectively. In preterm rats too, a marked increase in fetal ductus constriction was observed with the combined administration of these two drugs. Study of the dose effect of betamethasone revealed that maximal effects were obtained with 1 mg/kg of betamethasone combined with indomethacin in both preterm and near-term fetal rats. Increased constriction of the fetal ductus with combination treatment persisted from 1 to 8 h after administration. Administration of betamethasone 24 h before the rat was killed did not augment constriction of the fetal ductus by indomethacin administered 4 h before they were killed. Fetal ductus constriction by sulindac, another nonsteroidal antiinflammatory drug with little inhibitory effect on renal function, also was augmented by combined use with betamethasone (1 mg/kg). In conclusion, ductal constriction was markedly increased by combined administration of indomethacin and betamethasone in near-term and preterm fetal rats. (Pediatr Res 25:169-75, 1989) Abbreviations DA, ductus arteriosus PA, pulmonary artery Since the first reports (1, 2) on pharmacologic closure of the patent DA of preterm infants in 1976, indomethacin has been widely used to constrict the DA of the preterm infant. However, success rates of DA closure by indomethacin treatment in preterm infants were variable, indicating that therapy with indomethacin is less than perfect (3, 4). Our earlier study showed fetal ductal constriction by glucocorticoid hormones, including betamethasone (5). A subsequent study revealed that combined Received May 23, 1988; accepted September 13, 1988. Correspondence and reprint requests Kazuo Momma, The Heart Institute of Japan, Tokyo Women's Medical College, Kawadacho 8-1, Shinjukuku, Tokyo 162, Japan.Supported by grants from the Ministry of Education, Science, and Culture of Japan, the Welfare Ministry of Japan, the Japan Promotion Society for Cardiovascular Diseases and Japan Cardiovascular Research Foundation. 6administration of betamethasone and indomethacin markedly augments constriction of the fetal DA in both preterm and nearterm rats. MATERIALS AND METHODSVirgin Wistar rats (pregnancy period, 21.5 days) were mated overnight from 1700 to 900 h, and the presence of sperm on vaginal smears dated the 0 day of pregnancy. These rats were fed commercial solid food and water. Indomethacin (Sumitomo Chemical Co., Osaka, Japan) or sulindac (Merck-Banyu, Tokyo, Japan) was administered through an orogastric ...

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“…Assay for plasma indomethacin was carried out by the electron captive gas chromatographic method [10] at Merck, Sharp and Dohme Research Laboratory. The Student paired t test was used to compare variables before and after the study.…”

Section: Methodsmentioning

confidence: 99%

Does Indomethacin Affect the Control of Breathing in Premature Infants?

Wilks²

1989

Dev Pharmacol Ther

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The effect of indomethacin on the control of breathing was simultaneously evaluated in 10 premature infants who had significant patent ductus arteriosus and received indomethacin therapy. In an attempt to maintain high plasma level in these infants of advanced postnatal age (≥ 6 weeks), indomethacin was administered intravenously at a dosage of 0.3 mg/kg, at 8-hour intervals, for a total of three doses. Following indomethacin therapy, there was a significant increase in tidal volume, minute ventilation, tidal volume/inspiratory time and in airway pressure (P(0.1), P(max)) generated during airway occlusion. Seven infants required lower ventilatory rates after study. In spite of desirable plasma indomethacin level, there was no significant improvement in echo left atrium/aortic root dimension ratio, cardiovascular dysfunction score and in blood pH, PO(2) and PCO(2). None of the infants showed clinical evidence of ductus closure. The results of the study suggested that indomethacin may stimulate respiration and that endogenous prostaglandin may play a role in the regulation of breathing.

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Determination of indomethacin in serum and urine by electron-capture gas-liquid chromatography

Cited by 49 publications

References 8 publications

Indomethacin Therapy in Premature Infants with Patent Ductus Arteriosus - Determination of Therapeutic Plasma Levels

Indomethacin Therapy in Premature Infants with Patent Ductus Arteriosus - Determination of Therapeutic Plasma Levels

Increased Constriction of the Ductus Arteriosus with Combined Administration of Indomethacin and Betamethasone in Fetal Rats

Does Indomethacin Affect the Control of Breathing in Premature Infants?

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