TY - JOUR
T1 - Vaginal Diazepam for Nonrelaxing Pelvic Floor Dysfunction
T2 - The Pharmacokinetic Profile
AU - Larish, Alyssa M.
AU - Dickson, Rozalin R.
AU - Kudgus, Rachel A.
AU - McGovern, Renee M.
AU - Reid, Joel M.
AU - Hooten, W. Michael
AU - Nicholson, Wayne T.
AU - Vaughan, Lisa E.
AU - Burnett, Tatnai L.
AU - Laughlin-Tommaso, Shannon K.
AU - Faubion, Stephanie S.
AU - Green, Isabel C.
N1 - Publisher Copyright:
© 2019
PY - 2019/6
Y1 - 2019/6
N2 - Background: Vaginal diazepam is frequently used to treat pelvic floor tension myalgia and pelvic pain despite limited knowledge of systemic absorption. Aim: To determine the pharmacokinetic and adverse event profile of diazepam vaginal suppositories. Methods: We used a prospective pharmacokinetic design with repeated assessments of diazepam levels. Eight healthy volunteers were administered a 10-mg compounded vaginal diazepam suppository in the outpatient gynecologic clinic. Serum samples were collected at 0, 45, 90, 120, and 180 minutes; 8, 24, and 72 hours; and 1 week following administration of a 10-mg vaginal suppository. The occurrence of adverse events was assessed using the alternate step and tandem walk tests, the Brief Confusion Assessment Method, and numerical ratings. Plasma concentrations of diazepam and active long-acting metabolites were measured. Pharmacokinetic parameters were calculated by standard noncompartmental methods. Results: The mean peak diazepam concentration (Cmax) of 31.0 ng/mL was detected at a mean time (Tmax) of 3.1 hours after suppository placement. The bioavailability was found to be 70.5%, and the mean terminal elimination half-life was 82 hours. The plasma levels of temazepam and nordiazepam peaked at 0.8 ng/mL at 29 hours and 6.4 ng/mL at 132 hours, respectively. Fatigue was reported by 3 of 8 participants. Clinical Implications: Serum plasma concentrations of vaginally administered diazepam are low; however the half-life is prolonged. Strengths & Limitations: Strengths include use of inclusion and exclusion criteria aimed at mitigating clinical factors that could adversely impact diazepam absorption and metabolism, and the use of an ultrasensitive LC-MS/MS assay. Limitations included the lack of addressing the efficacy of vaginal diazepam in lieu of performing a pure pharmacokinetic study with healthy participants. Conclusion: Vaginal administration of diazepam results in lower peak serum plasma concentration, longer time to peak concentration, and lower bioavailability than standard oral use. Providers should be aware that with diazepam's long half-life, accumulating levels would occur with chronic daily doses, and steady-state levels would not be reached for up to 1 week. This profile would favor intermittent use to allow participation in physical therapy and intimacy. Larish AM, Dickson RR, Kudgus RA, et al. Vaginal Diazepam for Nonrelaxing Pelvic Floor Dysfunction: The Pharmacokinetic Profile. J Sex Med 2019;16;763–766.
AB - Background: Vaginal diazepam is frequently used to treat pelvic floor tension myalgia and pelvic pain despite limited knowledge of systemic absorption. Aim: To determine the pharmacokinetic and adverse event profile of diazepam vaginal suppositories. Methods: We used a prospective pharmacokinetic design with repeated assessments of diazepam levels. Eight healthy volunteers were administered a 10-mg compounded vaginal diazepam suppository in the outpatient gynecologic clinic. Serum samples were collected at 0, 45, 90, 120, and 180 minutes; 8, 24, and 72 hours; and 1 week following administration of a 10-mg vaginal suppository. The occurrence of adverse events was assessed using the alternate step and tandem walk tests, the Brief Confusion Assessment Method, and numerical ratings. Plasma concentrations of diazepam and active long-acting metabolites were measured. Pharmacokinetic parameters were calculated by standard noncompartmental methods. Results: The mean peak diazepam concentration (Cmax) of 31.0 ng/mL was detected at a mean time (Tmax) of 3.1 hours after suppository placement. The bioavailability was found to be 70.5%, and the mean terminal elimination half-life was 82 hours. The plasma levels of temazepam and nordiazepam peaked at 0.8 ng/mL at 29 hours and 6.4 ng/mL at 132 hours, respectively. Fatigue was reported by 3 of 8 participants. Clinical Implications: Serum plasma concentrations of vaginally administered diazepam are low; however the half-life is prolonged. Strengths & Limitations: Strengths include use of inclusion and exclusion criteria aimed at mitigating clinical factors that could adversely impact diazepam absorption and metabolism, and the use of an ultrasensitive LC-MS/MS assay. Limitations included the lack of addressing the efficacy of vaginal diazepam in lieu of performing a pure pharmacokinetic study with healthy participants. Conclusion: Vaginal administration of diazepam results in lower peak serum plasma concentration, longer time to peak concentration, and lower bioavailability than standard oral use. Providers should be aware that with diazepam's long half-life, accumulating levels would occur with chronic daily doses, and steady-state levels would not be reached for up to 1 week. This profile would favor intermittent use to allow participation in physical therapy and intimacy. Larish AM, Dickson RR, Kudgus RA, et al. Vaginal Diazepam for Nonrelaxing Pelvic Floor Dysfunction: The Pharmacokinetic Profile. J Sex Med 2019;16;763–766.
KW - Chronic Pelvic Pain
KW - Diazepam
KW - Dyspareunia
KW - Nonrelaxing Pelvic Floor Dysfunction
KW - Pelvic Floor Dysfunction
KW - Pelvic Pain
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UR - http://www.scopus.com/inward/citedby.url?scp=85064434763&partnerID=8YFLogxK
U2 - 10.1016/j.jsxm.2019.03.003
DO - 10.1016/j.jsxm.2019.03.003
M3 - Article
C2 - 31010782
AN - SCOPUS:85064434763
SN - 1743-6095
VL - 16
SP - 763
EP - 766
JO - Journal of Sexual Medicine
JF - Journal of Sexual Medicine
IS - 6
ER -