Pharmacokinetic Properties of a Sufentanil Sublingual Tablet Intended to Treat Acute Pain.
Background: Desirable product attributes for treatment of moderate-to-severe acute pain in many medically supervised settings are rapid onset and a route of administration not requiring intravenous access. The pharmacokinetic characteristics of sublingually administered tablets containing 15 or 30 µ...
| Publicado en: | Anesthesiology Vol. 128; no. 5; pp. 943 - 953 |
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| Autores principales: | , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Lippincott Williams & Wilkins
May2018
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=129094044&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 129094044 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00033022 1V8 jtl: Anesthesiology issn: 00033022 maglogo: N pubinfo: dt: May2018 vid: 128 iid: 5 pid: 433 pub: Lippincott Williams & Wilkins place: Baltimore, Maryland artinfo: ui: 129094044 129094044 NLM29498947 129094044 10.1097/ALN.0000000000002145 NLM29498947 129094044 ppf: 943 ppct: 10 formats: tig: atl: Pharmacokinetic Properties of a Sufentanil Sublingual Tablet Intended to Treat Acute Pain. aug: au: Fisher, Dennis M. Chang, Peter Wada, Russell Dahan, Albert Palmer, Pamela P. Wada, D Russell affil: P Less Than, San Francisco, California sug: subj: Analgesics, Opioid Pharmacokinetics Pain Drug Therapy Sufentanil Pharmacokinetics Human Biological Availability Oxidoreductases Antagonists and Inhibitors Young Adult Aged, 80 and Over Female Adult Middle Age Administration, Sublingual Aged Male Sufentanil Administration and Dosage Adolescence Tablets Validation Studies Comparative Studies Evaluation Research Multicenter Studies Scales Aged, 80 & over Adult: 19-44 years Middle Aged: 45-64 years Aged: 65+ years Adolescent: 13-18 years Female Male ab: Background: Desirable product attributes for treatment of moderate-to-severe acute pain in many medically supervised settings are rapid onset and a route of administration not requiring intravenous access. The pharmacokinetic characteristics of sublingually administered tablets containing 15 or 30 µg of sufentanil are described.Methods: Blood was sampled from healthy subjects (four studies, 122 subjects) and patients (seven studies, 944 patients). Studies in healthy subjects determined bioavailability, effect of inhibition of cytochrome P450 3A4, and the plasma concentration profile with single and hourly sublingual doses. Studies in patients evaluated effects of weight, age, sex, and organ impairment on apparent clearance. Noncompartmental and mixed-effect population methods were used.Results: Bioavailability of a single sublingual tablet was 52%, decreasing to 35% with repeat dosing. Ketoconazole (CYP3A4 inhibitor) increased maximum plasma concentration 19% and increased the area under the curve 77%. After a single 30-µg dose, plasma concentrations reached the published sufentanil analgesic threshold (24 pg/ml) within 30 min, peaked at 1 h, and then decreased below therapeutic concentrations by ~3 h. With hourly administration, plasma concentrations plateaued by the fifth dose. Time for concentrations to decrease 50% from maximal values was similar after 1 dose (2.5 ± 0.85 h) and 12 doses (2.5 ± 0.72 h). Clearance increased with weight, decreased with age, and was not affected by renal or hepatic impairment.Conclusions: The time course of a single 30-µg dose was consistent with onset of analgesia and redosing frequency observed in clinical trials. Sublingual sufentanil tablets provide the opportunity to noninvasively and rapidly treat moderate-to-severe pain in a monitored setting. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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