ISSN:
1573-904X
Keywords:
hyaluronan (hyaluronic acid)
;
metabolism
;
Michaelis–Menten kinetics
;
extraction ratio
;
modeling
;
turnover
;
sheep
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Hyaluronan (HA; hyaluronic acid) is produced in the interstitium and reaches the blood circulation through the lymph. It is rapidly eliminated by means of specific receptors on liver endothelium. The elimination characteristics of intravenously administered HA were studied in 10 conscious sheep at the normal plasma HA concentration by injection of a 3H-labeled tracer and at a very high concentration by an i.v. infusion of unlabeled HA and simultaneous injection of a tracer dose of 3H-labeled HA. At a normal plasma HA concentration (0.12 ± 0.05 µg/ml; range, 0.072–0.228 µg/ml), the apparent T 1/2 of 3H-HA was 5.3 ± 1.1 min (range, 3.3–6.5 min). At higher plasma concentrations (range, 1.83–3.35 µg/ml), the apparent T 1/2 was considerably prolonged (range, 18.2–43.5 min). A one-compartment, nonlinear model was fitted to data obtained from the bolus-infusion study of unlabeled HA. The Michaelis–Menten constant, K m , was 0.12 ± 0.04 µg/ml, indicating that a deviation from linear kinetics will occur when the normal plasma concentration is exceeded. The V max was 0.062 ± 0.009 µg/ml/min. Three-dimensional surface plots showed that the plasma HA concentration and the total hepatic plasma flow influence the apparent metabolic clearance, extraction ratio, turnover, and T 1/2 of intravenously injected hyaluronan. There was a high correlation between T 1/2 as measured by the injected 3H-HA and T 1/2 calculated from the model (r = 0.96).
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1015982204926
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