Plasma and cerebrospinal fluid concentrations of paracetamol after a single intravenous dose of propacetamol.

Abstract

Since the antipyretic and probably the analgesic effects of paracetamol are, at least in part, centrally mediated, its plasma and cerebrospinal fluid (CSF) concentrations were measured in 43 patients with nerve-root compression pain. Each subject was given a short i.v. infusion of 2 g propacetamol, a prodrug which is hydrolysed to paracetamol within 7 min. Single blood and CSF samples were drawn concomitantly in each patient at intervals between 20 min and 12 h. Maximum CSF drug concentrations were observed at the 4th hour, subsequent concentrations exceeding those in plasma. The elimination half-life of paracetamol calculated from pooled data was shorter in plasma (2.4 h) than in CSF (3.2 h). The time-course of paracetamol in CSF may parallel that of analgesic effect.

Novel pharmaceuticals in the management of postoperative pain

“…To avoid this slow and erratic uptake of oral acetaminophen in postsurgical patients, IV acetaminophen (paracetamol) has been used in Europe since 2001. PK studies of IV acetaminophen have demonstrated rapid CNS penetration in both adult and pediatric patients [5,6]. Recently, a comparative study of IV versus oral or rectal administration of acetaminophen demonstrated more rapid CNS drug concentrations and overall higher CNS exposure (area under the curve) for the IV route, based on cerebral spinal fluid sampling in six healthy male volunteers [7].…”

The Effect of Preemptive Lornoxicam, Paracetamol and Paracetamol Lornoxicam Combinations on the Quality of Patient-Controlled Analgesia After Abdominal Surgery

“…Paracetamol and NSAI drugs are well known for their effectiveness and have good safety profiles. Their individual use or combinations with opioids provide effective pain control for postoperative pain management [5,6]. The exact action mechanism of paracetamol has not been completely explained, however, it is thought to have an indirect effect on the serotonergic system through central COX3 inhibition of the central nervous system (CNS) [7].…”

Propacetamol as an alternative of ketorolac for postoperative pain management using patient-controlled analgesia

“…A gram of propacetamol infused intravenously hydrolyzes into 0.5 g of acetaminophen and pharmacologically inactive N,N-diethylglycine within 7 min [13][14][15]. Acetaminophen is widely used to control mild to moderate pain in clinical conditions and is well known for its inhibitory effect on central cyclooxygenase.…”