Experimental Pain in Healthy Human Subjects: Gender Differences in Nociception and in Response to Ibuprofen

Walker, Judith S.; Carmody, John

doi:10.1097/00132586-199908000-00058

Cited by 62 publications

(89 citation statements)

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“…be effective. To be able to detect analgesia, electrical pain stimulation needs to be intense and evoke pain intensity well above the pain detection threshold [17,18]. [19].…”

Section: Dosing Regimesmentioning

confidence: 99%

Assessing efficacy of non‐opioid analgesics in experimental pain models in healthy volunteers: an updated review

Staahl

Olesen

Arendt‐Nielsen

et al. 2009

Brit J Clinical Pharma

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AIMExperimental pain models may help to evaluate the mechanisms of analgesics and target the clinical indications for their use. This review, the second in a series of two, addresses how the efficacy of non-opioid analgesics have been assessed in human volunteers using experimental pain models. METHODSA literature search was completed for randomized controlled studies that included human experimental pain models, healthy volunteers and non-opioid analgesics. RESULTSNonsteroidal anti-inflammatory drugs worked against various types of acute pain as well as in hyperalgesia. Analgesia from paracetamol was difficult to detect in experimental pain and the pain needed to be assessed with very sensitive methods like evoked brain potentials. The N-methyl-D-aspartate antagonists exemplified by ketamine generally needed strong, long-lasting or repeated pain in the skin for detectable analgesia, whereas pain in muscle and viscera generally was more easily attenuated. Gabapentin worked well in several models, particularly those inducing hyperalgesia, whereas lamotrigine was weak in modulation of experimental pain. Imipramine attenuated pain in most experimental models, whereas amitriptyline had weaker effects. Delta-9-tetrahydrocannabinol attenuated pain in only a few models.

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“…be effective. To be able to detect analgesia, electrical pain stimulation needs to be intense and evoke pain intensity well above the pain detection threshold [17,18]. [19].…”

Section: Dosing Regimesmentioning

confidence: 99%

Assessing efficacy of non‐opioid analgesics in experimental pain models in healthy volunteers: an updated review

Staahl

Olesen

Arendt‐Nielsen

et al. 2009

Brit J Clinical Pharma

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show abstract

“…Numerous studies have examined the individual factors infl uencing pain perception using thermal, 6-9 cold pressor, 10,11 mechanical, 12 ischemic, 13, 14 chemical 15,16 or electrical [17][18][19] stimuli to provoke pain. However, these studies have limitations for clinical application because they were either laboratory-based or used only noninvasive noxious stimuli.…”

mentioning

confidence: 99%

Pain from intramuscular vaccine injection in adults

et al. 2012

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“…8 Opioids such as pentazocine show greater efficacy for pain relief in women, but the NSAID ibuprofen exhibits better responses in men with no sex-associated differences in kinetics. 9 Racial differences in pharmacokinetics of several drugs have been demonstrated. 10,11 White patients were found to have 50% higher methylprednisolone clearances than black patients in a sex-and age-matched study in renal transplant recipients.…”

mentioning

confidence: 99%

Prednisolone Pharmacokinetics and Pharmacodynamics in Relation to Sex and Race

Magee

Blum

Lates

et al. 2001

The Journal of Clinical Pharma

107

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Prednisolone pharmacokinetics (PK) and pharmacodynamics (PD) were investigated in relation to sex and race in white males, black males, white females, and black females (n = 8/group) after a single oral dose (0.27 mg/kg) of prednisone. The study consisted of baseline and prednisone phases with 32-hour sampling in each phase. Women were studied during the luteal phase of their menstrual cycle. Total and free plasma prednisolone concentrations were assayed by HPLC and ultrafiltration, and pharmacokinetic data were analyzed by compartmental fitting using WinNonlin. Plasma cortisol concentrations were assayed by HPLC; T-helper, T-suppressor lymphocyte, and neutrophil cell counts were determined by FACS and hemocytometry, and these pharmacodynamic data were evaluated by basic and extended indirect response models using ADAPT II. Total body weight-normalized free prednisolone oral clearance and apparent volume of distribution were higher in men compared with women, regardless of race (by22%in whites and40%in blacks for oral clearance, p < 0.01; by32%in whites and38% in blacks for apparent volume of distribution, p < 0.01). The 50% inhibitory concentration (IC 50 ) values for T-suppressor cell-trafficking inhibition were higher in whites than in blacks, regardless of sex (by 125% in men and 208% in women, p < 0.01). The IC 50 or SC 50 values for effects of prednisolone on cortisol secretion and T-helper lymphocyte or neutrophil trafficking were not statistically different between men and women, blacks and whites. The findings of this study suggest that there are some prednisolone PK/PD differences related to sex and race. However, these differences do not suggest the need for dosage adjustments, and additional experiments with repeat dosing are needed to fully evaluate the clinical implication of these findings.The role of sex as a factor in the pharmacokinetics and the pharmacodynamics (PK/PD) of drugs has become well appreciated. 1 Women often exhibit modestly more rapid clearances of drugs metabolized by the CYP3A4 pathway (e.g., methylprednisolone 2 ). They may also show alterations in the disposition of drugs in relation to the phase of the menstrual cycle (e.g., theophylline 3 ), pregnancy (e.g., caffeine 4 ), or after menopause (e.g., verapamil 5 ). Women receiving oral contraceptives are likely to show more rapid clearances of conjugated NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript drugs (e.g., oxazepam) but have reduced clearances of many oxidized compounds (e.g., prednisolone 6 ). Interpretation of data is sometimes complicated by the need to assess whether pharmacokinetic parameters are properly normalized for body weight differences and if the phase of the menstrual cycle was monitored.The assessment of pharmacodynamic differences between men and women requires control of pharmacokinetic factors and use of appropriate methodology to relate responses to plasma or biophase drug concentrations. There are some notable examples of marked sex differences in drug efficacy. As...

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Experimental Pain in Healthy Human Subjects: Gender Differences in Nociception and in Response to Ibuprofen

Cited by 62 publications

References 0 publications

Assessing efficacy of non‐opioid analgesics in experimental pain models in healthy volunteers: an updated review

Assessing efficacy of non‐opioid analgesics in experimental pain models in healthy volunteers: an updated review

Pain from intramuscular vaccine injection in adults

Prednisolone Pharmacokinetics and Pharmacodynamics in Relation to Sex and Race

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