Influence of Morbid Obesity on the Pharmacokinetics of Morphine, Morphine-3-Glucuronide, and Morphine-6-Glucuronide

Hoogd, Sjoerd de; Välitalo, Pyry A. J.; Dahan, Albert; Kralingen, Simone van; Coughtrie, Michael W.H.; Dongen, Eric P.A. van; Ramshorst, Bert van; Knibbe, Catherijne A. J.

doi:10.1007/s40262-017-0544-2

Cited by 43 publications

(34 citation statements)

References 40 publications

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“…One study noted decreased clearance of active morphine metabolites in morbidly obese compared to normal weight healthy volunteers, despite normal elimination of the parent compound. The clinical importance of this finding is unknown but could be of consequence with sustained dosing [23]. Pharmacodynamic alterations such as increased opioid sensitivity have also been described in select populations (e.g., geriatrics, obstructive sleep apnea) which can further increase the risk for respiratory depression [24,25].…”

Section: Analgesia Opioidsmentioning

confidence: 99%

Drug dosing in the critically ill obese patient—a focus on sedation, analgesia, and delirium

Erstad

Barletta

2020

Crit Care

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Practice guidelines provide clear evidence-based recommendations for the use of drug therapy to manage pain, agitation, and delirium associated with critical illness. Dosing recommendations however are often based on strategies used in patients with normal body habitus. Recommendations specific to critically ill patients with extreme obesity are lacking. Nonetheless, clinicians must craft dosing regimens for this population. This paper is intended to help clinicians design initial dosing regimens for medications commonly used in the management of pain, agitation, and delirium in critically ill patients with extreme obesity. A detailed literature search was conducted with an emphasis on obesity, pharmacokinetics, and dosing. Relevant manuscripts were reviewed and strategies for dosing are provided.

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Section: Analgesia Opioidsmentioning

confidence: 99%

Drug dosing in the critically ill obese patient—a focus on sedation, analgesia, and delirium

Erstad

Barletta

2020

Crit Care

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“…Many patients who require postoperative treatment of pain are obese and/or have diabetes mellitus. Previous studies have reported the effect of obesity and/or diabetes mellitus on the pharmacokinetics of many drugs [5–7]. Tramadol is an analgesic used for treating moderate to moderately severe acute and chronic pain.…”

Section: Introductionmentioning

confidence: 99%

Influence of Obesity and Type 2 Diabetes Mellitus on the Pharmacokinetics of Tramadol After Single Oral Dose Administration

Porażka

Szałek

Połom

et al. 2019

Eur J Drug Metab Pharmacokinet

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Background and Objectives The number of overweight, obese and diabetic patients is constantly increasing. Metabolic disorders may affect the pharmacokinetics of drugs, e.g., by altering the activity of cytochrome P450 (CYP) isoenzymes. Tramadol is a commonly used analgesic metabolised mainly via CYP2D6 to its active metabolite, O -desmethyltramadol. The aim of the study was to assess the influence of overweight, obesity and type 2 diabetes mellitus on tramadol and O -desmethyltramadol pharmacokinetics. Methods All patients received a single oral dose (100 mg) of tramadol. The plasma concentrations of tramadol and O -desmethyltramadol were measured with the validated high-performance liquid chromatography method with fluorescence detection. The pharmacokinetic parameters of tramadol and O -desmethyltramadol were calculated by non-compartmental methods. Results After nephrectomy, the patients were divided into four groups—a control group ( n = 12, mean [SD] age 61 [14] years, body mass index (BMI) 22 [2] kg/m 2 , CL cr (creatinine clearance) 74 [30] mL/min); an overweight group ( n = 15, mean [SD] age 63 [11] years, BMI 27 [1] kg/m 2 , CL cr 81 [35] mL/min); an obese group ( n = 12, mean [SD] age 57 [8] years, BMI 33 [4] kg/m 2 , CL cr 113 [51] mL/min); and an obese and diabetic group ( n = 9, mean [SD] age 64 [10] years, BMI 33 [4] kg/m 2 , CL cr 87 [35] mL/min). Apart from the time to first occurrence of maximal concentration ( t max) , there were no significant differences in the pharmacokinetic parameters of tramadol and O -desmethyltramadol among the groups. Moreover, there were no significant differences in the O -desmethyltramadol/tramadol ratios among the four groups of patients after nephrectomy. Conclusions No significant differences were found in the pharmacokinetics of tramadol and O -desmethyltramadol, indicating that the opioid can be administered to overweight, obese and diabetic patients without dosage adjustment.

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“…Based on previous studies on pharmacokinetics of morphine, 7,8 It was determined that 15 patients for each group were required for the study to have type I error of 0.05 and a power of 80%, using a confidence interval of 95%. We recruited 20 per group to account for patient drop out, random errors, and additional comparisons.…”

Section: Discussionmentioning

confidence: 99%

<p>Analgesic Effect of Morphine Added to Bupivacaine in Serratus Anterior Plane Block Following Modified Radical Mastectomy. Only a Local Effect? Randomized Clinical Trial</p>

Sherif¹,

El-Rahman²,

Othman³

et al. 2020

JPR

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Background: Serratus anterior plane (SAP) block, a novel regional anesthetic procedure, involves the anterolateral chest wall. Opioid receptors have been found on peripheral nerve terminals, so morphine may have a local action. Objective: This work aimed at exploring the analgesic efficacy of morphine added to bupivacaine in SAPB in patients for whom modified radical mastectomy was conducted and whether it is a mere local effect. Methods: Forty female patients were planned to have modified radical mastectomy participated in the study. Patients were randomly divided into two groups; Control group (C): received ultrasound-guided serratus anterior plane block with 20 mL of bupivacaine hydrochloride 0.25%; Morphine group (M): received the same in addition to 10 mg morphine sulfate. Intra-and postoperative blood samples were taken for the assessment of morphine serum levels. All patients were assessed for VAS scores during rest and movement (VAS-R and VAS-M). Time to the first request and the total amount of the rescue analgesia were recorded. Results: In group M, Morphine was not detected in the plasma of all patients. Both VAS-R and VAS-M were significantly higher in group C than in group M (P<0.001) and (P≤0.003), respectively. Time to the first request of rescue analgesia was 8.5 h in group C compared to 20 h in group M (P=0.005) with a median dose of acetaminophen consumption of 2 g in group C compared to 1 g in group M (P=0.006). Conclusion: Ten mg of morphine, when added to bupivacaine in SAPB, improved postoperative analgesia in patients to whom modified radical mastectomy was conducted. This effect seems to be attributed merely to local mechanisms. Registration: The registration number of this study is NCT02962024 at www.clinicaltrial. gov.

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Influence of Morbid Obesity on the Pharmacokinetics of Morphine, Morphine-3-Glucuronide, and Morphine-6-Glucuronide

Cited by 43 publications

References 40 publications

Drug dosing in the critically ill obese patient—a focus on sedation, analgesia, and delirium

Drug dosing in the critically ill obese patient—a focus on sedation, analgesia, and delirium

Influence of Obesity and Type 2 Diabetes Mellitus on the Pharmacokinetics of Tramadol After Single Oral Dose Administration

<p>Analgesic Effect of Morphine Added to Bupivacaine in Serratus Anterior Plane Block Following Modified Radical Mastectomy. Only a Local Effect? Randomized Clinical Trial</p>

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