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Dennis M Fisher

Publications and source records attributed to Dennis M Fisher.

5 recordsLinked to original sources
PubMed2004

Relative analgesic potency of fentanyl and sufentanil during intermediate-term infusions in patients after long-term opioid treatment for chronic pain.

Sufentanil, a potent mu-opioid agonist, historically has not been been given systemically to treat chronic pain. An implantable, fixed-rate osmotic pump that delivers sufentanil subcutaneously is being developed for this purpose. In that transdermal fentanyl may be a useful intermediary to estimate the appropriate sufentanil dose before implant, accurate information is needed about the relative analgesic potency of sufentanil and fentanyl during continuous infusion. To determine this relative potency, we administered these drugs to opioid-treated chronic pain patients using a target-controlled infusion (TCI). Sixty-three patients with stable chronic pain and daily oral opioid requirements equivalent to 100-1000 mg of morphine received TCI of fentanyl and sufentanil, each for a minimum of 16 h. Drug administration was double-blind and the order of administration was randomly assigned. Target concentration was changed until the patient reported that analgesia was adequate (defined as a pain level equal to or better than baseline). Seven patients did not complete the infusion and protocol violations invalidated data for 15 patients. For the remaining 41 patients, target concentrations associated with adequate analgesia were achieved for both sufentanil and fentanyl. The median value for the equianalgesic concentration ratio (steady-state fentanyl infusion to steady-state sufentanil infusion) was 7.5; mean potency ratio was 7.44 (95% confidence interval 6.8-8.2). During titrated, intermediate-term infusions in patients previously treated with opioids for chronic pain, sufentanil is approximately 7.5 times as potent as fentanyl.

Adult↗
PubMed2003

Pharmacokinetics of an implanted osmotic pump delivering sufentanil for the treatment of chronic pain.

BACKGROUND: A matchstick-sized implanted osmotic pump (Chronogesic) that delivers sufentanil subcutaneously for more than 90 days is being developed to treat chronic pain. This study evaluates pharmacokinetic characteristics related to the absorption of sufentanil using a prototype 60-day system. METHODS: Twelve opioid-naive volunteers were given naltrexone to prevent opioid effects. Sufentanil, 60 microg, was infused intravenously over 6 h, then 48 h later, the pump was implanted subcutaneously in the upper arm under local anesthesia. Pumps were removed 9 days later. In six volunteers, fever (1.6-3.3 degrees C) was induced with interleukin-2. Plasma was sampled and population pharmacokinetic modeling was performed to estimate in vivo release rate and absorption half-life. Bioavailability was calculated by comparing in vivo to in vitro release rates. The impact of perturbations in release rate on sufentanil plasma concentration (Cp) was simulated. RESULTS: Fever had no systematic effect on Cp. Release rate estimated in vivo was similar to that measured in vitro; bioavailability did not differ from 100%. Absorption half-life was 16.2 h. Simulation demonstrated that supplemental release of sufentanil from the implant (as might occur with local heating) increases Cp an average of 2.5-2.8% per hours supplemental dose. CONCLUSIONS: An implantable osmotic pump delivered sufentanil in vivo at the rate predicted from in vitro experiments. The rate at which sufentanil was absorbed from the subcutaneous space (half-life > 16 h) was markedly slower than reported with subcutaneous or intramuscular administration of large volumes of dilute opioids; this slow absorption dampens potential changes in Cp if release rate is perturbed.

Adult↗
PubMed2002

Pharmacodynamic modeling of muscle relaxants: effect of design issues on results.

BACKGROUND: Pharmacodynamic studies of muscle relaxants use different dosing regimens (such as administration by bolus vs. infusion and doses that produce complete vs. incomplete paralysis). The authors used published data to evaluate the effect of modeling assumptions on pharmacodynamic estimates. METHODS: The authors used a pharmacokinetic-pharmacodynamic dataset in which patients received cisatracurium, 75 or 300 microg/kg (1.5 or 6 x ED95), to generate plasma concentration (Cp) and twitch depression (effect) curves. They then evaluated the impact of the following: assuming that Cp decreased monotonically versus increasing initially before decreasing monotonically; misrecording effect data by 6 s or less; and doses targeting incomplete versus complete paralysis. Parameters evaluated were the steady state Cp depressing twitch tension 50% (C50) and the rate constant for equilibration between plasma and effect site concentrations (k(e0)). RESULTS: With the large dose, increasing the time at which Cp peaked from 0.0 to 1.5 min decreased C50 and increased k(e0) markedly; with the small dose, changes in both were small. Misrecording the timing of effect had a larger impact with the large dose compared with the small dose. Doses smaller than ED50 or those producing prolonged, complete twitch depression yielded biased and variable estimates. CONCLUSION: The erroneous assumption that Cp decreases monotonically after bolus administration affects accuracy of pharmacodynamic estimates with doses producing rapid, complete twitch depression. Other errors (e.g., misrecording the time of drug administration) impact on pharmacodynamic estimates, particularly with large doses. The authors' findings suggest that investigators performing neuromuscular (and other) pharmacodynamic studies should carefully consider the impact of study design on their parameter estimates.

Artifacts↗