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Analgesics

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Early Phase Drug Evaluation in Man

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Abstract

The aims of the early phase evaluation of a novel analgesic are to examine kinetics and limits to dosage by side-effects (tolerance), and to establish the therapeutic dose. Kinetics and tolerance studies are common to all novel drugs and are addressed elsewhere in this volume. This chapter will concentrate upon methods to establish efficacy, and then touch upon other pharmacodynamic properties of analgesics which can sometimes be explored.

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References

  • Beecher, H. K. (1957). The measurement of pain. Pharm. Rev., 9, 59–209

    CAS  PubMed  Google Scholar 

  • Bloomfield, S. S., Mitchell, J., Cissell, G. and Barden, T. P. (1986). Analgesic sensitivity of two post-partum pain models. Pain, 27, 171–9

    Article  CAS  PubMed  Google Scholar 

  • Bromm, B., Meier, W. and Scharein, E. (1986). Imipramine reduces experimental pain. Pain, 25, 245–57

    Article  CAS  PubMed  Google Scholar 

  • Bromm, B. and Scharein, E. (1982a). Response plasticity of pain evoked reactions in man. Physiol. Behav., 28, 109–16

    Article  CAS  PubMed  Google Scholar 

  • Bromm, B. and Scharein, E. (1982b). Principal component analysis of pain related cerebral potentials to mechanical and electrical stimulation in man. Electroenceph. Clin. Neurophysiol., 53, 94–103

    Article  CAS  PubMed  Google Scholar 

  • Buchsbaum, M. S., Davis, G. C., Coppola, R. and Naber, D. (1981a). Opiate pharmacology and individual differences. I. Psychophysical pain measurements. Pain, 10, 357–66

    Article  CAS  PubMed  Google Scholar 

  • Buchsbaum, M. S., Davis, G. C., Coppola, R. and Naber, D. (1981b). Opiate pharmacology and individual differences. II. Somatosensory evoked potentials. Pain, 10, 367–77

    Article  CAS  PubMed  Google Scholar 

  • Calimlin, J. F., Sriwatanakul, K., Wardell, W. M., Lasagna, L. and Cox, C. (1982). Analgesic efficacy of parenteral metkephamid acetate in the treatment of post operative pain. Lancet, i, 1374–5

    Article  Google Scholar 

  • Chapman, C. R., Casey, K. L., Dubner, R., Foley, K. M., Gracely, R. H. and Reading, A. E. (1985). Pain measurement: an overview. Pain, 22, 1–31

    Article  CAS  PubMed  Google Scholar 

  • Chudler, E. H. and Dong, W. K. (1983). The assessment of pain by cerebral evoked potentials. Pain, 16, 221–44

    Article  CAS  PubMed  Google Scholar 

  • Clissold, S. P. and Beresford, R. (1987). Proquazone. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in rheumatic diseases and pain states. Drugs, 33, 478–502

    Article  CAS  PubMed  Google Scholar 

  • De Jalon, P. D. G., Harrison, F. J. J., Johnson, K. I., Kozma, C. and Schnelle, K. (1985). A modified cold stimulation technique for the evaluation of analgesic activity in human volunteers. Pain, 22, 183–9

    Article  Google Scholar 

  • Deschamps, K., Band, P. R. and Coldman, A. J. (1988). Assessment of adult cancer pain: shortcomings of current methods. Pain, 32, 133–9

    Article  CAS  PubMed  Google Scholar 

  • Downing, J. W., Brock-Utne, J. G., Barclay, A. and Schwegmann, I. L. (1981). WY16225 (Dezocine) a new synthetic opiate agonist-antagonist and potent analgesic: comparison with morphine for relief of pain after lower abdominal surgery. Br. J. Anaesth., 53, 59–63

    Article  CAS  PubMed  Google Scholar 

  • Fernandes, de Lima, V. M., Chatrian, G. E., Lettich, E., Canfield, R. C., Miller, R. C. and Soso, M. J. (1982). Electrical stimulation of toothpulp in humans. I. Relationships among physical stimulus intensities, psychological magnitude estimates, and cerebral evoked potentials. Pain, 14, 207–32

    Article  Google Scholar 

  • Forster, C., Anton, F., Reeh, P. W., Weber, E. and Handwerker, H. O. (1988). Measurement of the analgesic effects of aspirin with a new experimental algesimetric procedure. Pain, 32, 215–22

    Article  CAS  PubMed  Google Scholar 

  • Frank, M., McAteer, E. J., Cattermole, R., Loughman, B., Stafford, L. B. and Hitchcock, A. M. (1987). Nalbuphine for obstetric analgesia. A comparison of nalbuphine with pethidine for pain relief in labour when administered by patient controlled analgesia (PCA). Anaesthesia, 42, 697–703

    Article  CAS  PubMed  Google Scholar 

  • Gracely, R. H. and Dubner, R. (1987). Reliability and validity of verbal descriptor scales of painfulness. Pain, 29, 175–85

    Article  CAS  PubMed  Google Scholar 

  • Gracely, R. H., Dubner, R. and McGrath, P. A. (1982). Fentanyl reduces the intensity of painful toothpulp sensations: controlling for detection of active drugs. Anesth. Analg., 61, 751–5

    Article  CAS  PubMed  Google Scholar 

  • Gracely, R. H., Lota, L., Walter, D. J. and Dubner, R. (1988). A multiple random staircase method of psychophysical pain assessment. Pain, 32, 55–63

    Article  CAS  PubMed  Google Scholar 

  • Hanks, G. W., Twycross, R. G. and Bliss, J. M. (1987). Controlled release morphine tablets; a double blind trial in patients with advanced cancer. Anaesthesia, 42, 840–4

    Article  CAS  PubMed  Google Scholar 

  • Harmer, M., Slattery, P. J., Rosen, M. and Vickers, M. D. (1983). Intramuscular on demand analgesia: double blind controlled trial of pethidine, buprenorphine, morphine and meptazinol. Br. Med. J., 286, 680–2

    Article  CAS  Google Scholar 

  • Holland, R. L., Harkin, N. E., Coleshaw, S. R. K., Jones, D. A., Peck, A. W. and Telekes, A. (1988). Dipipanone and nifedipine in cold induced pain: analgesia not due to skin warming. Br. J. Clin. Pharm., 24, 823–6

    Article  Google Scholar 

  • Honig, S. (1983). Long-term therapy for the pain of ostearthritis: a comparison of zomepirac sodium and aspirin. J. Clin. Pharm., 23, 494–504

    Article  CAS  Google Scholar 

  • Hougs, W. and Skouby, A. P. (1957). The analgetic action of analgetics antihistaminics and chlorpromazine on volunteers. Acta Pharm. Toxicol., 13, 405–9

    Article  CAS  Google Scholar 

  • Jasinsky, D. R. and Preston, K. L. (1985). Assessment of dezocine for morphine like subjective effects and miosis. Clin. Pharm. Ther., 38, 544–8

    Article  Google Scholar 

  • Jensen, M. P., Karoly, P. and Braver, S. (1986). The measurement of clinical pain intensity: a comparison of six methods. Pain, 27, 117–26

    Article  CAS  PubMed  Google Scholar 

  • Jones, S. F. and McQuay, H. J. (1987). Letter to Editor. Pain, 28, 265–6

    Article  CAS  PubMed  Google Scholar 

  • Keats, A. S. (1985). The effect of drugs on respiration in man. Ann. Rev. Pharm. Toxicol., 25, 41–65

    Article  CAS  PubMed  Google Scholar 

  • Kremer, F., Atkinson, J. H. and Ignelzi, R. J. (1981). Measurement of pain: patient preference does not confound pain measurement. Pain, 10, 241–8

    Article  CAS  PubMed  Google Scholar 

  • Levine, J. D., Gordon, N. C., Smith, R. and McBryde, R. (1986). Desipramine enhances opiate post operative analgesia. Pain, 21, 45–9

    Article  Google Scholar 

  • Littman, G. S., Walker, B. R. and Scheider, B. E. (1985). Reassessment of verbal and visual analogue ratings in analgesic studies. Clin. Pharm. Ther., 38, 16–23

    Article  CAS  Google Scholar 

  • McQuay, H. J., Poppleton, P., Carroll, D., Summerfield, R. J., Bullingham, R. E. S. and Moore, R. A. (1986). Ketorolac and acetaminophen for orthopaedic post operative pain. Clin. Pharm. Ther., 39, 89–93

    Article  CAS  Google Scholar 

  • Melzack, R. (1975). The McGill Pain Questionnaire: major properties and scoring methods. Pain., 1, 277–99

    Article  CAS  PubMed  Google Scholar 

  • O’Hara, D. A., Fragen, R. J., Kinzer, M. and Pemberton, D. (1987). Ketorolac tromethamine as compared with morphine sulfate for treatment of post operative pain. Clin. Pharm. Ther., 41, 556–61

    Article  Google Scholar 

  • Olstad, O. A. and Skjelbred, P. (1986). Comparison of the analgesic effect of a corticosteroid and paracetamol in patients with pain after oral surgery. Br. J. Clin. Pharm., 22, 437–42

    Article  CAS  Google Scholar 

  • Posner, J. (1984). A modified submaximal effort tourniquet test for evaluation of analgesics in healthy volunteers. Pain, 19, 143–51

    Article  CAS  PubMed  Google Scholar 

  • Preston, K. L., Bigelow, G. E. and Liebson, I. A. (1987). Comparative evaluation of morphine, pentazocine, and ciramadol in post addicts. J. Pharm. Exp. Ther., 240, 900–10

    CAS  Google Scholar 

  • Schady, W. and Torebjork, H. E. (1984). Central effects of zomepirac on pain evoked by intraneural stimulation in man. J. Clin. Pharm., 24, 429–35

    Article  CAS  Google Scholar 

  • Sechzer, P. H. (1977). Evaluation of fenoprofen as a post operative analgesic. Curr. Ther. Res., 21, 137–48

    CAS  PubMed  Google Scholar 

  • Seki, T. (1978). Evaluation of effect of acetyl-salicylic acid using electrical stimulation on the forefinger of healthy volunteers. Br. J. Clin. Pharm., 6, 521–4

    Article  CAS  Google Scholar 

  • Smith, G. M. and Beecher, H. K. (1969). Experimental production of pain in man: sensitivity of a new method to 600 mg of aspirin. Clin. Pharm. Ther., 10, 213–16

    CAS  Google Scholar 

  • Sriwatanakul, K., Kelvie, W., Lasagna, L., Calimlim, J. F., Weis, O. F. and Mehta, G. (1983). Studies with different types of visual analogue scales for measurement of pain. Clin. Pharm. Ther., 34, 234–9

    Article  CAS  Google Scholar 

  • Stacher, G., Bauer, P., Scheider, C., Winklehner, S. and Schmierer, S. (1982). Effects of a combination of oral naproxen sodium and codeine on experimentally induced pain. Eur. J. Clin. Pharm., 21, 485–90

    Article  CAS  Google Scholar 

  • Stacher, G., Steinringer, H., Schneider, S., Mittelbach, G., Gaupman, G., Abatzi, Th.-A. and Stacher-Janotta, G. (1987). Effects of graded doses of a new 5-hydroxytryptamine/noradrenaline uptake inhibitor (RO15-8081) in comparison with 60 mg codeine and placebo on experimentally induced pain and side effect profile in man. Br. J. Clin. Pharm., 24, 627–35

    Article  CAS  Google Scholar 

  • Stacher, G., Steinringer, H., Schneider, S., Mittelbach, G., Winklehner, S. and Gaupman, G. (1986). Experimental pain induced by electrical and thermal stimulation of the skin in healthy man: sensitivity to 75 and 150 mg diclofenac sodium in comparison with 60 mg codeine and placebo. Br. J. Clin. Pharm., 21, 35–43

    Article  CAS  Google Scholar 

  • Stambaugh, J. E. and McAdams, J. (1987). Comparison of intramuscular dezocine with butorphanol and placebo in chronic cancer pain: a method to evaluate analgesia after both single and repeated doses. Clin. Pharm. Ther., 42, 210–19

    Article  Google Scholar 

  • Sunshine, A., Zighelboim, I., Laska, E., Siegel, C., Olson, N. Z. and DeCastro, A. (1986). A double blind parallel comparison of ketoprofen, aspirin and placebo in patients with post partum pain. J. Clin. Pharm., 26, 706–11

    Article  CAS  Google Scholar 

  • Telekes, A., Holland, R. L. and Peck, A. W. (1987). Indomethacin: effects on cold induced pain and the nervous system in healthy volunteers. Pain, 30, 321–8

    Article  CAS  PubMed  Google Scholar 

  • Warren, M. M., Boyce, W. H., Evans, J. W. and Peters, P. C. (1985). A double blind comparison of dezocine and morphine in patients with acute renal and ureteral colic. J. Urol., 134, 457–9

    CAS  PubMed  Google Scholar 

  • Willer, J. C. (1985). Studies on pain. Effects of morphine on a spinal nociceptive flexion reflex and related pain sensation in man. Brain Res., 331, 105–14

    Article  CAS  PubMed  Google Scholar 

  • Wolff, B. B., Kantor, T. G. and Cohen, P. (1976). Laboratory pain induction methods for human analgesic assays. Adv. Pain Res. Ther., 1, 363–7

    Google Scholar 

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Author information

Authors and Affiliations

  1. Dept of Clinical Research, Duphar BV, PO Box 900, 1380 DA, Weesp, The Netherlands

    R. L. Holland

Authors
  1. R. L. Holland
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Editor information

Editors and Affiliations

  1. May and Baker Pharmaceuticals Rhône-Poulenc Ltd, Dagenham, RM10 7XS, UK

    John O’Grady MD, FRCP (Medical Director, Visiting Professor of Clinical Pharmacology) (Medical Director, Visiting Professor of Clinical Pharmacology)

  2. University of Vienna, Austria

    John O’Grady MD, FRCP (Medical Director, Visiting Professor of Clinical Pharmacology) (Medical Director, Visiting Professor of Clinical Pharmacology)

  3. Clinical Development Unit 1, The Upjohn Company, Kalamazoo, MI, 49001, USA

    Otto I. Linet MD, PhD (Director) (Director)

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© 1990 The editors and contributors

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Holland, R.L. (1990). Analgesics. In: O’Grady, J., Linet, O.I. (eds) Early Phase Drug Evaluation in Man. Palgrave, London. https://doi.org/10.1007/978-1-349-10705-6_52

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  • DOI: https://doi.org/10.1007/978-1-349-10705-6_52

  • Publisher Name: Palgrave, London

  • Print ISBN: 978-1-349-10707-0

  • Online ISBN: 978-1-349-10705-6

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