Oxycodone is an effective analgesic for the treatment of labour pain, according to the doctoral thesis of Mari Kinnunen, Lic Med.
Oxycodone is a semi-synthetic opioid derived from thebaine. Global consumption of oxycodone has surpassed that of morphine, which was for long considered as the ‘gold standard’ opioid. Oxycodone is assumed to be efficient in labour pain, as it is highly effective in visceral pain, however, data in this indication is scarce. Kinnunen’s thesis consists of a systematic review of oxycodone, a preclinical study of oxycodone in pregnant ewes and a clinical study of oxycodone in labour pain. The main objectives of the study were to evaluate pharmacokinetics of epidural and intravenous oxycodone administered to pregnant ewes, assess foetal/neonatal exposure to oxycodone and its metabolites, and evaluate analgesic efficacy of subcutaneous oxycodone in the latent phase of labour.
The systematic review found significant data of interactions with CYP3A inducers and inhibitors, which include, e.g., certain antibiotics and antifungals. Second, auspicious abuse-deterrent oxycodone formulations have been developed to reduce misuse of prescribed oxycodone. Third, oxycodone passes freely through the placenta and thus foetus is exposed to oxycodone. Oxycodone accumulates to mother’s milk in lactating women, and therefore lactating is not recommended if mother is using oxycodone for any prolonged periods. Last, a careful dose titration is necessary also in other vulnerable patient groups, e.g. neonates and elderly.
In the experimental study, 30 pregnant ewes received oxycodone either intravenously or epidurally. Paired blood samples were collected from the ewe and foetus, and plasma concentrations of oxycodone and its metabolites were analysed with an ultra-performance liquid chromatography mass spectrometry system. After epidural administration, drug concentrations in the spinal cord, brain, cerebrospinal fluid and plasma were analysed.
In the prospective clinical study, 76 parturients received subcutaneous oxycodone according to the hospital protocol in the latent phase of labour. Pain intensity was evaluated with a numerical rating scale after the first subcutaneous oxycodone dose of 0.1 mg/kg. At birth, blood samples from the umbilical and maternal veins were collected. Apgar scores and adverse effects were recorded.
The first novel finding of present study was that oxymorphone, an active oxycodone metabolite, concentrations in the foetal plasma were relatively high after maternal oxycodone administration. This was observed in experimental and clinical studies. However, in the study group of 76 parturients, no opioid-related neonatal adverse effects were observed. Second, epidural administration of oxycodone to sheep resulted in very high spinal oxycodone concentrations. This indicates that analgesia after epidural administration of oxycodone is provided mostly via direct spinal effect rather than systemic effect.
The doctoral thesis of Mari Kinnunen, Licentiate of Medicine, entitled Oxycodone in labour analgesia: pharmacokinetics, central nervous system concentrations and foetal exposure, will be examined at the Faculty of Health Sciences, University of Eastern Finland. The public examination will be held in Finnish at Kuopio Campus on 21 August 2020. The Opponent in the public examination will be Docent Kai Kiviluoma of the University of Oulu, and the Custos will be Docent Merja Kokki of the University of Eastern Finland.
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