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The following message was posted to: PharmPK
I appreciate if anybody can guide me in doing or reference to a PK-PD study
in acute pain model preferably dental pain.
Thank you,
Prasad Tata
Mallinckrodt, Inc.
St. Louis, MO
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[Two replies - db]
From: "Melethil, Srikumaran K."
Date: Fri, 19 Oct 2001 14:01:49 -0500
To: david.-at-.boomer.org
Subject: RE: PharmPK PK-PD Studies in pain
The following message was posted to: PharmPK
Prasad,
One of our former students (Sammy J. Hutcheson, PhD, 1993) worked on a
project titled " PD modeling of the analgesic properties of specific
non-opioid analgesics using the pain dental model". You should be able
to get the PhD thesis thru' our library. Please contact me if I can be
of additional help.
Sri
Srikumaran K. Melethil, Ph.D., JD (2001)
Professor, Pharmaceutics and Medicine
University of Missouri- Kansas City
203B Katz Hall (School of Pharmacy)
Kansas City, MO 64110
Phone: voice- 816-235-1794; fax - 816-235-5190
---
From: "Sam Liao"
Date: Fri, 19 Oct 2001 19:49:45 -0400
To: david.at.boomer.org
Subject: Re: PharmPK PK-PD Studies in pain
The following message was posted to: PharmPK
Hi Prasad:
Yes, there is a well established population PK/PD model for acute dental
pain originally published by Dr. Lew Sheiner and later expanded by Dr. Jaap
Mandema and Don Stanski (see abstract below). We had used this model in one
of our analgesic NDA submission successfully.
Best regards,
Sam Liao, Ph.D.
PharMax Research
270 Kerry Lane,
Blue Bell, PA 19422
phone: 215-6541151
efax: 1-720-2946783
Clin Pharmacol Ther 1996 Dec;60(6):619-35 Related Articles, Books,
LinkOut
Population pharmacodynamic model for ketorolac analgesia.
Mandema JW, Stanski DR.
Department of Anesthesia, Stanford University School of Medicine.
OBJECTIVE: To derive a population pharmacokinetic-pharmacodynamic model that
characterizes the distribution of pain relief scores and remedication times
observed in patients receiving intramuscular ketorolac for the treatment of
moderate to severe postoperative pain. BACKGROUND: The data analysis
approach deals with the complexities of analyzing analgesic trial data: (1)
repeated measurements, (2) ordered categorical response variables, and (3)
nonrandom censoring because the patients can take a rescue medication if
their pain relief is insufficient. METHODS: Patients (n = 522) received a
single oral or intramuscular administration of placebo or a single
intramuscular dose of 10, 30, 60, or 90 mg ketorolac for postoperative pain
relief. Pain relief was measured periodically with use of a five-category
ordinal scale up to 6 hours after dosing. In this period, 288 patients
received additional medication because of insufficient pain relief.
Pharmacokinetic data was available for 85 subjects. Models were fitted to
the data with the NONMEM program. RESULTS: The pharmacokinetic data was best
described by a two-compartment model with first-order absorption. Pain
relief was found to be a function of drug concentration (Emax model), time
(waxing and waning of placebo effect), and an individual random effect. The
drug concentration at half-maximal effect (EC50) and the first-order rate
constant (keo) half-life for pain relief were 0.37 mg/L and 24 minutes. The
probability of remedication was found to be a function of the observed level
of pain relief and was found to increase with time. Monte Carlo simulations
showed that adequate pain relief was achieved in 50% of the patients at 41,
27, 23, and 21 minutes after 10, 30, 60, or 90 mg of intramuscular
ketorolac. Adequate pain relief was maintained up to 6 hours in 50%, 70%,
78%, and 81% of patients after these four doses. Only 25% of the patients
achieved adequate pain relief with placebo. CONCLUSIONS: A population
pharmacokinetic-pharmacodynamic model for the analgesic efficacy of
intramuscular ketorolac was derived. The simulated relationship between
dose, time, and percentage of patients with adequate pain relief suggested
that 30 mg intramuscular ketorolac was the optimal initial dose for
postoperative pain relief.
Publication Types:
a.. Clinical Trial
b.. Controlled Clinical Trial
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The following message was posted to: PharmPK
Prasad:
We might be able to help you if we knew which aspect of the dental
model is of interest to you and we could certainly do the study if needed
because our hospital does a great many Wisdom tooth removals.
We have been studying pain models for some time, including Phase 1
first and second pain models. Our new infra-red laser method has
compared onset times from two formulations of acetominophen and we
achieved coefficients of variation down to 2% in only 12 subjects, so it is
very sensitive indeed. We have a Phase 2, mild, stable chronic pain in
osteoarthritic knees that detects topical NSAIDs very well. We have also
used a model of severe postoperative pain using a pca for both active
and placebo groups where one outcome measure is the amount of pca
the patients give themselves.
On dental pain models, our psychologist, Shaun Kilminster published last
year a survey of his new Short Pain Inventory (SPI) in two dental clinics
and two chronic severe medical clinics which gives considerable insight
into the populations involved. The SPI is a self administered
questionnaire similar in structure to the well known Spielberger rating
scale for anxiety. It examines mood changes in pain and stress and the
effect of analgesics. Items include fatigue, irritability, depression,
sadness. The reference is: Int J Pharm Med 2000, 14: 137-147 and we
could fax it to you if you like.
If you would let us know more about the nature of your enquiry, we'd be
glad to help with advice or information at the least.
Andrew Sutton MD(London).
Guildford Clinical Pharmacology
asutton.at.gcpl.co.uk
+44 (0) 1483 tel: 406886, fax: 455375
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