Sustained release of papaverine for the treatment of cerebral vasospasm: in vitro evaluation of release kinetics and biological activity

Dan S. Heffez M.D., F.R.C.S.1 and Kam W. Leong Ph.D.1
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  • 1 Departments of Neurosurgery and Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland
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✓ Cerebral vasospasm remains an unpredictable and inadequately treated complication of aneurysmal subarachnoid hemorrhage. To date, pharmacological treatment has been plagued in part by an inability to attain sufficiently high concentrations of vasodilator drug in the cerebrospinal fluid without precipitating systemic side effects such as hypotension. To circumvent this limitation of current pharmacological therapy, the authors have developed a sustained-release preparation of papaverine that can be implanted intracranially at the time of surgery for aneurysm clipping. In vitro evaluation of drug-release kinetics has demonstrated that reliable, sustained release of effective amounts of papaverine is possible. An in vitro bioassay using isolated preparations of canine basilar artery has confirmed the biological activity of this preparation. These in vitro studies are described.

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  • 1.

    Adams HP Jr, , Kassell NF, & Torner JC, et al: Predicting cerebral ischemia after aneurysmal subarachnoid hemorrhage: influences of clinical condition. CT results, and antifibrinolytic therapy. A report of the Cooperative Aneurysm Study. Neurology 37:15861591, 1987 Adams HP Jr, Kassell NF, Torner JC, et al: Predicting cerebral ischemia after aneurysmal subarachnoid hemorrhage: influences of clinical condition. CT results, and antifibrinolytic therapy. A report of the Cooperative Aneurysm Study. Neurology 37:1586–1591, 1987

    • Search Google Scholar
    • Export Citation
  • 2.

    Allen GS, , Ahn HS, & Preziosi TJ, et al: Cerebral arterial spasm — a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med 308:619624, 1983 Allen GS, Ahn HS, Preziosi TJ, et al: Cerebral arterial spasm — a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med 308:619–624, 1983

    • Search Google Scholar
    • Export Citation
  • 3.

    Allen GS, & Gross CJ: Cerebral arterial spasm. Part 7: In vitro effects of alpha adrenergic agents on canine arteries from six anatomical sites and six blocking agents on serotonin-induced contractions of the canine basilar artery. Surg Neurol 6:6370, 1976 Allen GS, Gross CJ: Cerebral arterial spasm. Part 7: In vitro effects of alpha adrenergic agents on canine arteries from six anatomical sites and six blocking agents on serotonin-induced contractions of the canine basilar artery. Surg Neurol 6:63–70, 1976

    • Search Google Scholar
    • Export Citation
  • 4.

    Allen GS, , Henderson LM, & Chou SN, et al: Cerebral arterial spasm. Part I: In vitro contractile activity of vasoactive agents on canine basilar and middle cerebral arteries. J Neurosurg 40:433441, 1974 Allen GS, Henderson LM, Chou SN, et al: Cerebral arterial spasm. Part I: In vitro contractile activity of vasoactive agents on canine basilar and middle cerebral arteries. J Neurosurg 40:433–441, 1974

    • Search Google Scholar
    • Export Citation
  • 5.

    Brown LR, , Wei CL, & Langer R: In vivo and in vitro release of macromolecules from polymeric drug delivery systems. J Pharm Sci 72:11811185, 1983 Brown LR, Wei CL, Langer R: In vivo and in vitro release of macromolecules from polymeric drug delivery systems. J Pharm Sci 72:1181–1185, 1983

    • Search Google Scholar
    • Export Citation
  • 6.

    Budavari S (ed): The Merck Index. Rahway, NJ: Merck & Co, 1989, p 1111 Budavari S (ed): The Merck Index. Rahway, NJ: Merck & Co, 1989, p 1111

    • Search Google Scholar
    • Export Citation
  • 7.

    Fisher CM, , Kistler JP, & Davis JM: Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 6:19, 1980 Fisher CM, Kistler JP, Davis JM: Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 6:1–9, 1980

    • Search Google Scholar
    • Export Citation
  • 8.

    Gioia AE, , White RP, & Bakhtian B, et al: Evaluation of the efficacy of intrathecal nimodipine in canine models of chronic cerebral vasospasm. J Neurosurg 62:721728, 1985 Gioia AE, White RP, Bakhtian B, et al: Evaluation of the efficacy of intrathecal nimodipine in canine models of chronic cerebral vasospasm. J Neurosurg 62:721–728, 1985

    • Search Google Scholar
    • Export Citation
  • 9.

    Heffez DS, & Passonneau JV: Effect of nimodipine on cerebral metabolism during ischemia and recirculation in the Mongolian gerbil. J Cereb Blood Flow Metab 5:523528, 1985 Heffez DS, Passonneau JV: Effect of nimodipine on cerebral metabolism during ischemia and recirculation in the Mongolian gerbil. J Cereb Blood Flow Metab 5:523–528, 1985

    • Search Google Scholar
    • Export Citation
  • 10.

    Kuwayama A, , Zervas NT, & Shintani A, et al: Papaverine hydrochloride and experimental hemorrhagic cerebral arterial spasm. Stroke 3:2733, 1972 Kuwayama A, Zervas NT, Shintani A, et al: Papaverine hydrochloride and experimental hemorrhagic cerebral arterial spasm. Stroke 3:27–33, 1972

    • Search Google Scholar
    • Export Citation
  • 11.

    Langer R, & Folkman J: Sustained release of macromolecules from polymers. Adv Exp Med Biol 47:175196, 1973 Langer R, Folkman J: Sustained release of macromolecules from polymers. Adv Exp Med Biol 47:175–196, 1973

    • Search Google Scholar
    • Export Citation
  • 12.

    Levy MI, & Giannotta SL: Induced hypertension and hypervolemia for the treatment of cerebral vasospasm. Neurosurg Clin North Am 1:357365, 1990 Levy MI, Giannotta SL: Induced hypertension and hypervolemia for the treatment of cerebral vasospasm. Neurosurg Clin North Am 1:357–365, 1990

    • Search Google Scholar
    • Export Citation
  • 13.

    Ljunggren B, , Brandt L, & Saveland H, et al: Outcome in 60 consecutive patients treated with early aneurysm operation and intravenous nimodipine. J Neurosurg 61:864873, 1984 Ljunggren B, Brandt L, Saveland H, et al: Outcome in 60 consecutive patients treated with early aneurysm operation and intravenous nimodipine. J Neurosurg 61:864–873, 1984

    • Search Google Scholar
    • Export Citation
  • 14.

    Mayberg MR, , Okada T, & Bark DH: Morphologic changes in cerebral arteries after subarachnoid hemorrhage. Neurosurg Clin North Am 1:417432, 1990 Mayberg MR, Okada T, Bark DH: Morphologic changes in cerebral arteries after subarachnoid hemorrhage. Neurosurg Clin North Am 1:417–432, 1990

    • Search Google Scholar
    • Export Citation
  • 15.

    Meyer FB: Calcium antagonists and vasospasm. Neurosurg Clin North Am 1:367376, 1990 Meyer FB: Calcium antagonists and vasospasm. Neurosurg Clin North Am 1:367–376, 1990

    • Search Google Scholar
    • Export Citation
  • 16.

    Ogata M, , Marshall BM, & Lougheed WM: Observations on the effects of intrathecal papaverine in experimental vasospasm. J Neurosurg 38:2025, 1973 Ogata M, Marshall BM, Lougheed WM: Observations on the effects of intrathecal papaverine in experimental vasospasm. J Neurosurg 38:20–25, 1973

    • Search Google Scholar
    • Export Citation
  • 17.

    Petruk KC, , West M, & Mohr G, et al: Nimodipine treatment in poor-grade aneurysm patients. Results of a multicenter double-blind placebo-controlled trial. J Neurosurg 68:505517, 1988 Petruk KC, West M, Mohr G, et al: Nimodipine treatment in poor-grade aneurysm patients. Results of a multicenter double-blind placebo-controlled trial. J Neurosurg 68:505–517, 1988

    • Search Google Scholar
    • Export Citation
  • 18.

    Pickard JD, , Murray GD, & Illingworth R, et al: Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British Aneurysm Nimodipine Trial. Br Med J 298:636642, 1989 Pickard JD, Murray GD, Illingworth R, et al: Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British Aneurysm Nimodipine Trial. Br Med J 298:636–642, 1989

    • Search Google Scholar
    • Export Citation
  • 19.

    Rhine WD, , Hsieh DS, & Langer R: Polymers for sustained macromolecule release: procedures to fabricate reproducible delivery systems and controlled release kinetics. J Pharm Sci 69:265270, 1980 Rhine WD, Hsieh DS, Langer R: Polymers for sustained macromolecule release: procedures to fabricate reproducible delivery systems and controlled release kinetics. J Pharm Sci 69:265–270, 1980

    • Search Google Scholar
    • Export Citation
  • 20.

    Simeone FA, & Trepper P: Cerebral vasospasm with infarction. Stroke 3:449455, 1972 Simeone FA, Trepper P: Cerebral vasospasm with infarction. Stroke 3:449–455, 1972

    • Search Google Scholar
    • Export Citation
  • 21.

    Smith RR, , Clower BR, & Peeler DF Jr, et al: The angiopathy of subarachnoid hemorrhage: angiographic and morphologic correlates. Stroke 14:240245, 1983 Smith RR, Clower BR, Peeler DF Jr, et al: The angiopathy of subarachnoid hemorrhage: angiographic and morphologic correlates. Stroke 14:240–245, 1983

    • Search Google Scholar
    • Export Citation
  • 22.

    Varsos VG, , Liszczak TM, & Han DH, et al: Delayed cerebral vasospasm is not reversible by aminophylline, nifedipine, or papaverine in a “two-hemorrhage” canine model. J Neurosurg 58:1117, 1983 Varsos VG, Liszczak TM, Han DH, et al: Delayed cerebral vasospasm is not reversible by aminophylline, nifedipine, or papaverine in a “two-hemorrhage” canine model. J Neurosurg 58:11–17, 1983

    • Search Google Scholar
    • Export Citation
  • 23.

    Voldby B, , Petersen OF, & Buhl M, et al: Reversal of cerebral arterial spasm by intrathecal administration of a calcium antagonist (nimodipine). An experimental study. Acta Neurochir 70:243254, 1984 Voldby B, Petersen OF, Buhl M, et al: Reversal of cerebral arterial spasm by intrathecal administration of a calcium antagonist (nimodipine). An experimental study. Acta Neurochir 70:243–254, 1984

    • Search Google Scholar
    • Export Citation

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