Methods and findings in experimental and clinical pharmacology
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Methods Find Exp Clin Pharmacol · May 2007
Urinary metabolites to assess in vivo ontogeny of hepatic drug metabolism in early neonatal life.
In addition to size-dependent allometric metabolic activity, most isoenzymes display age-dependent isoenzyme-specific ontogeny. We therefore need probe drugs to describe isoenzyme-specific ontogeny to develop more sophisticated, physiologically based models. We illustrate the feasibility and the relevance of in vivo assessment of hepatic metabolism, based on observations on urinary elimination of paracetamol and tramadol metabolites in neonates. ⋯ During repeated administration of intravenous paracetamol, it was documented that, in addition to postmenstrual and postnatal age (PNA), repeated administration also contributed to the urinary excretion of glucuronidated paracetamol. In both probe drugs evaluated, age only in part explained the interindividual variability observed. Urine metabolites to assess in vivo metabolism of drugs routinely administered in neonates likely increase both the feasibility and clinical relevance of studies on in vivo isoenzyme-specific ontogeny in neonates.
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Methods Find Exp Clin Pharmacol · May 2007
The effects of opioids, local anesthetics and adjuvants on isolated pregnant rat uterine muscles.
Local anaesthetics, opioids and adjuvants are often used for managing labor pain. Some others of these agents are reported to cause alterations on uterine contractility during labor. However, there are controversies and the effects of some others are unknown. ⋯ The findings of the present study demonstrated that some local anesthetics, opioids and adjuvants caused significant and agent-specific alterations on contractility of the pregnant rat myometrium. Therefore, they seemed to have a potential to influence uterine contractility during clinical management of pain during labor. However, further research is needed to extrapolate these finding to clinical practice.