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Plasma disappearance of ovine corticotrophin-releasing factor in man
Abstract:
Disappearance of immunoreactive ovine corticotrophin-releasing factor (IR-oCRF) from plasma after a single intravenous injection of ovine corticotrophin-releasing factor (oCRF) was studied in man in the morning and evening. Synthetic oCRF (80 micrograms) was injected intravenously to four normal male volunteers at 0900 h or at 2200 h. Blood samples were drawn before and 2, 5, 10, 15, 30, 45, 60, 90 and 120 min after the oCRF injection. Plasma IR-oCRF was measured by a specific radioimmunoassay for OCRF. Plasma concentrations of IR-oCRF after oCRF injections in the morning and in the evening did not differ significantly (P greater than 0.05). Disappearance of IR-oCRF was modelled with a two-exponent function by using a non-linear least squares computer program. The metabolic clearance rate, the apparent initial volume of distribution, the plasma half-life for the fast component and that for the slow component calculated from all eight tests in the morning and evening were 1.49 +/- 0.05 ml/min X kg, 44.4 +/- 1.7 ml/kg, 6.8 +/- 0.7 min and 46.2 +/- 2.3 min (mean +/- SEM), respectively. This relatively long half-life may be responsible for the prolonged biological effect of oCRF administered intravenously. There were no significant differences between parameters of IR-oCRF disappearance curves in the morning and those in the evening (P greater than 0.05).
Insights
The study found that the body clears immunoreactive ovine corticotrophin-releasing factor (IR-oCRF) similarly, regardless of whether it
Area of Science:
- Endocrinology
- Pharmacokinetics
- Neuroscience
Background:
- Ovine corticotrophin-releasing factor (oCRF) plays a crucial role in the stress response.
- Understanding the pharmacokinetic profile of oCRF is essential for its therapeutic applications.
- Previous studies have not fully elucidated the diurnal variations in oCRF metabolism.
Purpose of the Study:
- To investigate the disappearance kinetics of immunoreactive ovine corticotrophin-releasing factor (IR-oCRF) from human plasma.
- To determine if time of day (morning vs. evening) affects the metabolism of intravenously administered oCRF.
- To characterize key pharmacokinetic parameters of oCRF in healthy male volunteers.
Main Methods:
- Four healthy male volunteers received an intravenous injection of synthetic oCRF (80 micrograms).
- Blood samples were collected at multiple time points (2-120 minutes) post-injection.
- Plasma IR-oCRF levels were quantified using radioimmunoassay, and disappearance curves were analyzed using a two-exponent function and non-linear least squares regression.
Main Results:
- Plasma concentrations and disappearance rates of IR-oCRF did not significantly differ between morning and evening injections.
- Key pharmacokinetic parameters, including metabolic clearance rate (1.49 ml/min/kg) and plasma half-lives (fast: 6.8 min, slow: 46.2 min), were determined.
- The observed long half-life suggests a potentially prolonged biological effect of intravenous oCRF.
Conclusions:
- The metabolism and clearance of intravenously administered oCRF in humans are not significantly influenced by the time of day.
- The pharmacokinetic profile of oCRF, characterized by a relatively long terminal half-life, may contribute to its sustained biological activity.
- These findings provide valuable insights into the pharmacokinetics of oCRF, relevant for its clinical use and further research.