Purpose: To describe the modification of the ropivacaine (R) pharmacokinetics produced by the addition of epinephrine (E).
Methods: After Institutional Review Board approval, 18 ASA I boys received a caudal block (1 mL x kg(-1)) with either plain 0.2% R (Group E-) or with 0.2% R containing E (5 microg x mL(-1); Group E+). Venous blood samples were taken at zero, 15, 30, 60, 90, 120, 180, 240, 420, 720, 1440 min after caudal injection. Total R concentration in plasma was determined by high pressure liquid chromatography. Maximal concentration (C(max)) and time to peak concentration (T(max)) were obtained from the data, terminal half-life (T(1/2z)), clearance (Cl) and volume of distribution (Vd) were estimated by a non-compartmental approach. Subsequently, in order to determine the absorption rate (Ka) and to reduce to number of blood samples, 25 other children, receiving plain R and another group of 25 receiving the E solution were studied using a population approach (NONMEM). A one compartment model with first order absorption was used. The effect of weight, age and E on Cl, Vd and Ka was estimated.
Results: C(max) was significantly lower in Group E+ (0.93 mg x L(-1) +/- 0.29 vs 0.61 mg x L(-1) +/- 0.28, P = 0.05) and T(max) occurred later (124 min +/- 53 vs 47 min +/- 16, P = 0.003). Weight was a significant covariate for Cl and Vd while E significantly slowed R Ka [Group I Ka 0.025 min(-1) [coefficient of variation (CV) 21%] vs 0.078 min(-1) (CV 25%) in Group II].
Conclusion: The addition of E significantly modifies the pharmacokinetics of R injected caudally.
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Background: Down syndrome (DS, trisomy 21) is the most frequent genetic cause of intellectual disability (ID), prevalent in approximately 1 in 900 live births (Loane et al., 2013). People with DS are at high risk to develop Alzheimer's disease dementia (AD) (Lott & Head, 2001).
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Department of Chemistry and Biochemistry, Villanova University, Villanova, PA 19085, USA. Electronic address:
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Department of Emergency Medicine, University of California San Francisco, San Francisco, California, USA.
Coingestion of cardiovascular drugs with angiotensin-converting enzyme inhibitors (ACEIs) can be associated with refractory shock derangements complicated by vasopressor resistance, prompting the use of novel, unconventional, or uncommonly used agents. A young adult male presented to the emergency department (ED) 10 h after ingesting lisinopril and amlodipine. On arrival, he was hypotensive with a blood pressure of 72/39 mmHg.
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