A Sensitive Radioimmunoassay (Ria) for Clonidine

Arndts, D.; Stähle, H.; Darda, S.; Lohmann, Herman J.; Überbacher, J.

doi:10.1016/b978-0-08-023768-8.50120-1

Cited by 4 publications

(5 citation statements)

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“…Clonidine is metabolized to five metabolites including the following: p-hydroxy-clonidine; dichlorophenylguanidine; 1-(2,6-dichloro-4-hydroxyphenyl)-guanidine; 2-[(2,6-dichlorophenyl)-imino]-imidazolidine-4-one; and 2-[2,6-dichloro-4-hydroxyphenyl)-imino]-imidazolidine-4-one (Darda et al, 1978). The primary metabolite ( p-hydroxyclonidine) of clonidine is Ͻ10% of unchanged drug in the urine from nonpregnant subjects (Darda et al, 1978;Arndts et al, 1979). The metabolites of clonidine have been reported to be inactive (Lowenthal, 1980).…”

Section: Clonidine Pharmacokinetics In Pregnancymentioning

confidence: 99%

Clonidine Pharmacokinetics in Pregnancy

Buchanan¹,

Easterling²,

Carr³

et al. 2008

Drug Metab Dispos

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ABSTRACT:The objective of this study was to determine the pharmacokinetic parameters of clonidine during pregnancy compared with previously published data in nonpregnant subjects. Serial blood and urine samples were collected in 17 women during mid to late pregnancy over one steady-state dosing interval to determine clonidine noncompartmental pharmacokinetic parameters (n ‫؍‬ 17) and creatinine clearance. In six of these pregnant subjects, maternal and umbilical cord (venous and arterial) plasma samples were collected at the time of delivery for measurement of clonidine concentrations. Clonidine apparent oral clearance was found to be 440 ؎ 168 ml/min during pregnancy compared with 245 ؎ 72 ml/min as previously reported in nonpregnant subjects (p < 0.0001) (Cunningham et al., 1994). There was a strong correlation (r ‫؍‬ 0.82, p < 0.001) between clonidine renal clearance, adjusted for variation in glomerular filtration rate, and urine pH. Umbilical cord to maternal plasma clonidine concentration ratios were 1.0 ؎ 0.1 (arterial) and 1.0 ؎ 0.1 (venous). In conclusion, clonidine is cleared more rapidly in pregnant women than in nonpregnant subjects. At the time of delivery, the fetus is exposed to similar plasma clonidine concentrations as the mother.Chronic hypertension during pregnancy is associated with complications, including fetal growth restriction, premature birth, preeclampsia, placental abruption, hypertensive crisis, and in some cases fetal demise. Very little information is available on the pharmacokinetic changes that occur for antihypertensive medications during pregnancy. Clonidine, a centrally acting, ␣-2 adrenergic agonist, has been used for the treatment of hypertension during pregnancy (Kobinger, 1978;Hartikainen-Sorri et al., 1987). In the nonpregnant population, approximately 60% of clonidine is eliminated unchanged by the kidneys (Davies et al., 1977). There are significant changes in kidney function during pregnancy, with creatinine clearance reported to increase by 50 to 60% (Davison and Noble, 1981). The pharmacokinetics of clonidine have not been studied during pregnancy. The objective of this study was to characterize the pharmacokinetics of clonidine during pregnancy. Materials and MethodsAfter receiving written informed consent from patients, we examined steady-state pharmacokinetics of orally administered clonidine in the plasma of 17 pregnant women receiving clonidine during mid pregnancy (22-26 weeks gestation) or late pregnancy (34 -38 weeks gestation). Six of these women participated in maternal and umbilical cord (arterial and venous) plasma sample collections at the time of delivery for measurement of clonidine concentrations. Gestational age was based on the last menstrual period or early ultrasound dating.Subject Selection. This study was approved by the University of Washington Investigational Review Board. Subjects were eligible to participate if they were pregnant, 18 years of age, had a hematocrit Ն28%, and were receiving oral clonidine for maternal hypertension. Dosing Regi...

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Section: Clonidine Pharmacokinetics In Pregnancymentioning

confidence: 99%

Clonidine Pharmacokinetics in Pregnancy

Buchanan¹,

Easterling²,

Carr³

et al. 2008

Drug Metab Dispos

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“…(12)(13)(14)(15). Assays with these antibodies were conducted as usually described for drug-specific RIAs: (a) accuracy was determined with biological fluids (serum, urine) with added known levels of drugs; (b) so-called "matrix effects" were abolished in the assays by dilutions of analytical samples in biological fluids identical to those used for calibration curves, except that they were drug free; (c) specificity of RIAs was generally assessed by determining cross-reactivities of drug metabolites; (d) pharmacokinetics in human plasma were studied after oral or intravenous administration of clonidine.…”

Section: Resultsmentioning

confidence: 99%

“…Serum (15)(16)(17)(18)(19)(20) Sample preparation. All the samples tested in this study were prepared without any blood-clotting inhibitors and after fasting (10 h).…”

Section: Methodsmentioning

confidence: 99%

A circulating substance cross-reacting with antiimidazoline antibodies. Detection in serum in relation to essential hypertension.

Dontenwill

Molines²,

Verdun³

et al. 1993

J. Clin. Invest.

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It has been shown in various mammal species that clonidine, a well known centrally acting hypotensive agent, acts through the activation of imidazoline receptors (IRs) in the nucleus reticularis lateralis (NRL) of the brainstem. Specific binding sites sensitive to imidazolines and insensitive to catecholamines have been detected in rat and bovine, as well as human brains. An endogenous ligand, other than catecholamines, should exist for these IRs. Such a ligand could play a role in the pathophysiology of human essential hypertension. Therefore, we developed two RIAs with polyclonal and monoclonal anticlonidine antibodies. These antibodies presented specificity spectra similar to that of the IRs: they bound imidazolines and not catecholamines at all. These RIAs were used to detect imidazoline-like immunoreactivity in the human serum. Immunoreactive substance was measured in 26 normotensive subjects' sera, and specificity of interaction between antibodies and sera was verified. None of the known endogenous substances tested so far were able to interact with the two antibodies. Immunoreactivity in 32 essential hypertensive patients' sera proved higher in -30% of cases. Values of immunoreactivity positively correlated with the mean arterial pressure values. This study demonstrates the existence of an "imidazoline-like" immunoreactive substance in the human serum with high levels in some hyper-

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“…in urine (Darda et al 1978;Arndts et al 1979;Buchanan et al 2009). At least one population pharmacokinetic study has been published in children and adolescents (0-15 years of age) who received CLON-IR by intravenous, rectal, and epidural administration during anesthesia, which determined that by 1 year of age, 82% of the adult clearance rate is achieved (Potts et al 2007).…”

Section: Pharmacokineticsmentioning

confidence: 97%