Prospective evaluation of the pharmacodynamics of piritramide in neonates and infants

Abstract

Piritramide is a synthetic opioid commonly used in Germany and Austria for the analgesia of pediatric patients. Little pharmacokinetic and pharmacodynamic data for the pediatric population is available. The aim of this investigation was to gain pharmacodynamic data on postsurgical analgesia and the side effects of piritramide. The study was approved by the Ethics Committee of the Medical Faculty. Data were collected in an open, prospective clinical trial. After obtaining the parents' informed written consent, patients received a bolus of piritramide 50 mug/kg for postsurgical analgesia or to prevent pain resulting from invasive procedures. Titration doses of 15 microg/kg were allowed. Vital signs and pain intensity were closely monitored. Data from 39 patients could be included in the analysis. Of the patients, 95% were in the immediate postsurgical course, 5% had piritramide for invasive procedures, and 46% of the patients were ventilated. The mean piritramide dosage was 64 +/- 24 microg/kg. Pharmacodynamic analysis showed adequate analgesia for at least 50% of the spontaneously breathing patients for 120 min after piritramide bolus. More than 50% of the ventilated patients showed inadequate analgesia at any point in time after piritramide bolus. Fifty-nine percent (59%) of the ventilated patients received additive analgesia versus 31% of spontaneously breathing patients. No relevant changes of vital signs could be observed. One patient received naloxone for apnea. We conclude that dosages of more than 50-70 microg/kg are needed for sufficient analgesia in ventilated postsurgical infants. In spontaneously breathing patients, 50-70 microg/kg provides a 120-min period of analgesia for more than 50% of patients. Cardiovascular stability of the patients was good and, with one exception, there was no respiratory depression.

Quantification of piritramide in human colostrum

“…The samples of 6 of 10 patients were all below LLOQ. Taking into account the amount of colostrum consumed by the newborn (3–5 mL/kg/day), the maximal dose orally ingested by the neonate is more than 100 times lower than the recommended paediatric intravenous dose for therapy of post‐operative pain . In their study, Müller et al .…”

“…Taking into account the amount of colostrum consumed by the newborn (3-5 mL/kg/day), 24 the maximal dose orally ingested by the neonate is more than 100 times lower than the recommended paediatric intravenous dose for therapy of post-operative pain. 5,10 In their study, M€ uller et al 10 showed prolonged elimination and decreased total clearance of piritramide in newborns, which may lead to accumulation. These pharmacokinetic data in newborns were however obtained under diseased conditions.…”

“…It is a lipophilic (logP = 3·9) compound with two basic functions (pKa 1 = 5·4; pKa 2 = 7·3), and it binds highly to proteins (~94%). It has been shown to have full μ‐opioid receptor activity . The pharmacokinetics of piritramide in adults has been well described .…”

“…[6][7][8][9] In newborns, a higher initial concentration and a distinct prolongation of the elimination half-life of piritramide compared to infants, young children and adults were shown. 10 The authors concluded that the dosage to treat postoperative pain in newborns should therefore be reduced and the dosing intervals should be adapted to at least 6 h. 5,10 Elimination of this opioid drug is almost entirely dependent on hepatic metabolism. 8 As no information is available about the possible transfer of this opioid drug into breastmilk, breastfeeding is not always recommended.…”

“…It has been shown to have full l-opioid receptor activity. 5 The pharmacokinetics of piritramide in adults has been well described. [6][7][8][9] In newborns, a higher initial concentration and a distinct prolongation of the elimination half-life of piritramide compared to infants, young children and adults were shown.…”