Clinical Pharmacokinetics

, Volume 45, Issue 12, pp 1153–1176 | Cite as

Pharmacology of Drugs Formulated with DepoFoam™

A Sustained Release Drug Delivery System for Parenteral Administration Using Multivesicular Liposome Technology
  • Martin S. AngstEmail author
  • David R. Drover
Review Article


Lamellar liposome technology has been used for several decades to produce sustained-release drug formulations for parenteral administration. Multivesicular liposomes are structurally distinct from lamellar liposomes and consist of an aggregation of hundreds of water-filled polyhedral compartments separated by bi-layered lipid septa. The unique architecture of multivesicular liposomes allows encapsulating drug with greater efficiency, provides robust structural stability and ensures reliable, steady and prolonged drug release.

The favourable characteristics of multivesicular liposomes have resulted in many drug formulations exploiting this technology, which is proprietary and referred to as DepoFoam™. Currently, two formulations using multivesicular liposome technology are approved by the US FDA for clinical use, and many more formulations are at an experimental developmental stage. The first clinically available formulation contains the antineoplastic agent cytarabine (DepoCyt™) for its intrathecal injection in the treatment of malignant lymphomatous meningitis. Intrathecal injection of DepoCyt™ reliably results in the sustained release of cytarabine and produces cytotoxic concentrations in cerebrospinal fluid (CSF) that are maintained for at least 2 weeks. Early efficacy data suggest that DepoCyt™ is fairly well tolerated, and its use allows reduced dosing frequency from twice a week to once every other week and may improve the outcome compared with frequent intrathecal injections of unencapsulated cytarabine. The second available formulation contains morphine (DepoDur™) for its single epidural injection in the treatment of postoperative pain. While animal studies confirm that epidural injection of DepoDur™ results in the sustained release of morphine into CSF, the CSF pharmacokinetics have not been determined in humans. Clinical studies suggest that the use of DepoDur™ decreases the amount of systemically administered analgesics needed for adequate postoperative pain control. It may also provide superior pain control during the first 1–2 postoperative days compared with epidural administration of unencapsulated morphine or intravenous administration of an opioid. However, at this timepoint the overall clinical utility of DepoDur™ has yet to be defined and some safety concerns remain because of the unknown CSF pharmacokinetics of DepoDur™ in humans.

The versatility of multivesicular liposome technology is reflected by the many agents including small inorganic and organic molecules and macromolecules including proteins that have successfully been encapsulated. Data concerning many experimental formulations containing antineoplastic, antibacterial and antiviral agents underscore the sustained, steady and reliable release of these compounds from multivesicular liposomes after injection by the intrathecal, subcutaneous, intramuscular, intraperitoneal and intraocular routes. Contingent on the specific formulation and manufacturing process, agents were released over a period of hours to weeks as reflected by a 2- to 400-fold increase in elimination half life. Published data further suggest that the encapsulation process preserves bioactivity of agents as delicate as proteins and supports the view that examined multivesicular liposomes were non-toxic at studied doses. The task ahead will be to examine whether the beneficial structural and pharmacokinetic properties of multivesicular liposome formulations will translate into improved clinical outcomes, either because of decreased drug toxicity or increased drug efficacy.


Morphine Cytarabine Intrathecal Injection Epidural Injection Epidural Administration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.


  1. 1.
    Kim S, Turker MS, Chi EY, et al. Preparation of multivesicular liposomes. Biochem Biophys Acta 1983; 728: 339–48PubMedCrossRefGoogle Scholar
  2. 2.
    Mantripragada S. DepoFoam technology for sustained release injectable drug delivery. Drug Delivery Systems and Sciences 2001; 1: 13–6Google Scholar
  3. 3.
    Mantripragada S. A lipid based depot (DepoFoam technology) for sustained release drug delivery. Prog Lipid Res 2002; 41(5): 392–406PubMedCrossRefGoogle Scholar
  4. 4.
    Xiao C, Qi X, Maitani Y, et al. Sustained release of cisplatin from multivesicular liposomes: potentiation of antitumor efficacy against S180 murine carcinoma. J Pharm Sci 2004; 93(7): 1718–24PubMedCrossRefGoogle Scholar
  5. 5.
    Murry DJ, Blaney SM. Clinical pharmacology of encapsulated sustained-release cytarabine. Ann Pharmacother 2000; 34(10): 1173–8PubMedCrossRefGoogle Scholar
  6. 6.
    Chowdhary S, Chamberlain M. Leptomeningeal metastases: current concepts and management guidelines. J Natl Compr Canc Netw 2005; 3(5): 693–703PubMedGoogle Scholar
  7. 7.
    Fleischhack G, Jaehde U, Bode U. Pharmacokinetics following intraventricular administration of chemotherapy in patients with neoplastic meningitis. Clin Pharmacokinet 2005; 44(1): 1–31PubMedCrossRefGoogle Scholar
  8. 8.
    Howell SB. Clinical applications of a novel sustained-release injectable drug delivery system: DepoFoam technology. Cancer J 2001; 7(3): 219–27PubMedGoogle Scholar
  9. 9.
    Spector MS, Zasadzinski JA, Sankaram MB. Topology of multivesicular liposomes, a model biliquid foam. Langmuir 1996; 12(20): 4704–8CrossRefGoogle Scholar
  10. 10.
    Ellena JF, Le M, Cafisco DS, et al. Distribution of phopsholipids and triglycerides in multivesicular lipid particles. Drug Deliv 1999; 6(2): 97–106CrossRefGoogle Scholar
  11. 11.
    Kohn FR, Malkmus SA, Brownson EA, et al. Fate of the predominant phospholipid component of DepoFoam drug delivery matrix after intrathecal administration of sustainedrelease encapsulated cytarabine in rats. Drug Delivery Systems and Sciences 1998; 5: 143–51CrossRefGoogle Scholar
  12. 12.
    Yanez AM, Wallace M, Ho R, et al. Touch-evoked agitation produced by spinally administered phospholipid emulsion and liposomes in rats: structure-activity relation. Anesthesiology 1995; 82(5): 1189–98PubMedCrossRefGoogle Scholar
  13. 13.
    Wallace MS, Yanez AM, Ho RJ, et al. Antinociception and side effects of liposome-encapsulated alfentanil after spinal delivery in rats. Anesth Analg 1994; 79(4): 778–86PubMedCrossRefGoogle Scholar
  14. 14.
    Isackson J, Wallace MS, Ho RJ, et al. Antinociception and side effects of L- and D-dipalmitoylphosphatidyl choline liposomeencapsulated alfentanil after spinal delivery in rats. Pharmacol Toxicol 1995; 77(5): 333–40PubMedCrossRefGoogle Scholar
  15. 15.
    Ramprasad MP, Amini A, Kararli T, et al. The sustained granulopoietic effect of progenipoietin encapsulated in multivesicular liposomes. Int J Pharm 2003; 261(1–2): 93–103PubMedCrossRefGoogle Scholar
  16. 16.
    Langsten MV, Ramprasad MP, Kararli TT, et al. Modulation of the sustained delivery of myelopoietin (Leridistim) encapsulated in multivesicular liposomes (DepoFoam). J Control Release 2003; 89(1): 87–99CrossRefGoogle Scholar
  17. 17.
    Zhong H, Deng Y, Wang X, et al. Multivesicular liposome formulation for the sustained delivery of breviscapine. Int J Pharm 2005; 301(1–2): 15–24PubMedCrossRefGoogle Scholar
  18. 18.
    Kim S, Howell SB. Multivesicular liposomes containing cytarabine entrapped in the presence of hydrochloric acid for intracavitary chemotherapy. Cancer Treat Rep 1987; 71(7–8): 705–11PubMedGoogle Scholar
  19. 19.
    Viscusi ER. DepoDur: a new drug formulation with unique safety considerations [newsletter]. Indianapolis (IN): Anesthesia Patient Safety Foundation, 2005: 50–1Google Scholar
  20. 20.
    Chatelut E, Suh P, Kim S. Sustained-release methotrexate for intracavitary chemotherapy. J Pharm Sci 1994; 83(3): 429–32PubMedCrossRefGoogle Scholar
  21. 21.
    Katre NV, Asherman J, Schaefer H, et al. Multivesicular liposome (DepoFoam) technology for the sustained delivery of insulin-like growth factor-I (IGF-I). J Pharm Sci 1998; 87(11): 1341–6PubMedCrossRefGoogle Scholar
  22. 22.
    Gambling D, Hughes T, Martin G, et al. A comparison of Depodur, a novel, single-dose extended-release epidural morphine, with standard epidural morphine for pain relief after lower abdominal surgery. Anesth Analg 2005; 100(4): 1065–74PubMedCrossRefGoogle Scholar
  23. 23.
    Roy R, Kim S. Multivesicular liposomes containing bleomycin for subcutaneous administration. Cancer Chemother Pharmacol 1991; 28(2): 105–8PubMedCrossRefGoogle Scholar
  24. 24.
    Chatelut E, Kim T, Kim S. A slow-release methotrexate formulation for intrathecal chemotherapy. Cancer Chemother Pharmacol 1993; 32(3): 179–82PubMedCrossRefGoogle Scholar
  25. 25.
    Bonetti A, Chatelut E, Kim S. An extended-release formulation of methotrexate for subcutaneous administration. Cancer Chemother Pharmacol 1994; 33(4): 303–6PubMedCrossRefGoogle Scholar
  26. 26.
    Assil KK, Lane J, Weinreb RN. Sustained release of the antimetabolite 5-fluorouridine-5′-monophosphate by multivesicular liposomes. Ophthalmic Surg 1988; 19(6): 408–13PubMedGoogle Scholar
  27. 27.
    Assil KK, Hartzer M, Weinreb RN, et al. Liposome suppression of proliferative vitreoretinopathy: rabbit model using antimetabolite encapsulated liposomes. Invest Ophthalmol Vis Sci 1991; 32(11): 2891–7PubMedGoogle Scholar
  28. 28.
    Gariano RF, Assil KK, Wiley CA, et al. Retinal toxicity of the antimetabolite 5-fluorouridine 5′-monophosphate administered intravitreally using multivesicular liposomes. Retina 1994; 14(1): 75–80PubMedCrossRefGoogle Scholar
  29. 29.
    Grayson LS, Hansbrough JF, Zapata-Sirvent RL, et al. Pharmacokinetics of DepoFoam gentamicin delivery system and effect on soft tissue infection. J Surg Res 1993; 55(5): 559–64PubMedCrossRefGoogle Scholar
  30. 30.
    Grayson LS, Hansbrough JF, Zapata-Sirvent R, et al. Soft tissue infection prophylaxis with gentamicin encapsulated in multivesicular liposomes: results from a prospective, randomized trial. Crit Care Med 1995; 23(1): 84–91PubMedCrossRefGoogle Scholar
  31. 31.
    Roehrborn AA, Hansbrough JF, Gualdoni B, et al. Lipid-based slow-release formulation of amikacin sulfate reduces foreign body-associated infections in mice. Antimicrob Agents Chemother 1995; 39(8): 1752–5PubMedCrossRefGoogle Scholar
  32. 32.
    Huh J, Chen JC, Furman GM, et al. Local treatment of prosthetic vascular graft infection with multivesicular liposome-encapsulated amikacin. J Surg Res 1998; 74(1): 54–8PubMedCrossRefGoogle Scholar
  33. 33.
    Assil KK, Frucht-Perry J, Ziegler E, et al. Tobramycin liposomes: single subconjunctival therapy of pseudomonal keratitis. Invest Ophthalmol Vis Sci 1991; 32(13): 3216–20PubMedGoogle Scholar
  34. 34.
    Frucht-Perry J, Assil KK, Ziegler E, et al. Fibrin-enmeshed tobramycin liposomes: single application topical therapy of Pseudomonas keratitis. Cornea 1992; 11(5): 393–7PubMedCrossRefGoogle Scholar
  35. 35.
    Jain SK, Jain RK, Chourasia MK, et al. Design and development of multivesicular liposomal depot delivery system for controlled systemic delivery of acyclovir sodium. AAPS Pharm-SciTech 2005; 6(1): E35–41CrossRefGoogle Scholar
  36. 36.
    Kim S, Scheerer S, Geyer MA, et al. Direct cerebrospinal fluid delivery of an antiretroviral agent using multivesicular liposomes. J Infect Dis 1990; 162(3): 750–2PubMedCrossRefGoogle Scholar
  37. 37.
    Bonetti A, Kim S. Pharmacokinetics of an extended-release human interferon alpha-2b formulation. Cancer Chemother Pharmacol 1993; 33(3): 258–61PubMedCrossRefGoogle Scholar
  38. 38.
    Qiu J, Wei XH, Geng F, et al. Multivesicular liposome formulations for the sustained delivery of interferon alpha-2b. Acta Pharmacol Sin 2005; 26(11): 1395–401PubMedCrossRefGoogle Scholar
  39. 39.
    Li H, An JH, Park JS, et al. Multivesicular liposomes for oral delivery of recombinant human epidermal growth factor. Arch Pharm Res 2005; 28(8): 988–94PubMedCrossRefGoogle Scholar
  40. 40.
    Ramprasad MP, Anantharamaiah GM, Garber DW, et al. Sustained-delivery of an apolipoprotein E-peptidomimetic using multivesicular liposomes lowers serum cholesterol levels. J Control Release 2002; 79(1–3): 207–18PubMedCrossRefGoogle Scholar
  41. 41.
    Kaplan JG, DeSouza TG, Farkash A, et al. Leptomeningeal metastases: comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias. J Neurooncol 1990; 9(3): 225–9PubMedCrossRefGoogle Scholar
  42. 42.
    Zimm S, Collins JM, Miser J, et al. Cytosine arabinoside cerebrospinal fluid kinetics. Clin Pharmacol Ther 1984; 35(6): 826–30PubMedCrossRefGoogle Scholar
  43. 43.
    Bleyer WA, Dedrick RL. Clinical pharmacology of intrathecal methotrexate: I. Pharmacokinetics in nontoxic patients after lumbar injection. Cancer Treat Rep 1977; 61(4): 703–8PubMedGoogle Scholar
  44. 44.
    Graham FL, Whitmore GF. The effect of 1-beta-D-arabinofuranosylcytosine on growth, viability, and DNA synthesis of mouse L-cells. Cancer Res 1970; 30(11): 2627–35PubMedGoogle Scholar
  45. 45.
    Kim S, Kim DJ, Howell SB. Modulation of the peritoneal clearance of liposomal cytosine arabinoside by blank liposomes. Cancer Chemother Pharmacol 1987; 19(4): 307–10PubMedCrossRefGoogle Scholar
  46. 46.
    Kim S, Howell SB. Multivesicular liposomes containing cytarabine for slow-release Sc administration. Cancer Treat Rep 1987; 71(5): 447–50PubMedGoogle Scholar
  47. 47.
    Kim S, Kim DJ, Geyer MA, et al. Multivesicular liposomes containing 1-beta-D-arabinofuranosylcytosine for slow-release intrathecal therapy. Cancer Res 1987; 47(15): 3935–7PubMedGoogle Scholar
  48. 48.
    Kim S, Khatibi S, Howell SB, et al. Prolongation of drug exposure in cerebrospinal fluid by encapsulation into DepoFoam. Cancer Res 1993; 53(7): 1596–8PubMedGoogle Scholar
  49. 49.
    Kim S, Chatelut E, Kim JC, et al. Extended CSF cytarabine exposure following intrathecal administration of DTC 101. J Clin Oncol 1993; 11(11): 2186–93PubMedGoogle Scholar
  50. 50.
    Chamberlain MC, Khatibi S, Kim JC, et al. Treatment of leptomeningeal metastasis with intraventricular administration of depot cytarabine (DTC 101): a phase I study. Arch Neurol 1993; 50(3): 261–4PubMedCrossRefGoogle Scholar
  51. 51.
    Chamberlain MC, Kormanik P, Howell SB, et al. Pharmacokinetics of intralumbar DTC-101 for the treatment of leptomeningeal metastases. Arch Neurol 1995; 52(9): 912–7PubMedCrossRefGoogle Scholar
  52. 52.
    Bomgaars L, Geyer JR, Franklin J, et al. Phase I trial of intrathecal liposomal cytarabine in children with neoplastic meningitis. J Clin Oncol 2004; 22(19): 3916–21PubMedCrossRefGoogle Scholar
  53. 53.
    Glantz MJ, LaFollette S, Jaeckle KA, et al. Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis. J Clin Oncol 1999; 17(10): 3110–6PubMedGoogle Scholar
  54. 54.
    Glantz MJ, Jaeckle KA, Chamberlain MC, et al. A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. Clin Cancer Res 1999; 5(11): 3394–402PubMedGoogle Scholar
  55. 55.
    Jaeckle KA, Phuphanich S, Bent MJ, et al. Intrathecal treatment of neoplastic meningitis due to breast cancer with a slowrelease formulation of cytarabine. Br J Cancer 2001; 84(2): 157–63PubMedCrossRefGoogle Scholar
  56. 56.
    Cole BF, Glantz MJ, Jaeckle KA, et al. Quality-of-life-adjusted survival comparison of sustained-release cytosine arabinoside versus intrathecal methotrexate for treatment of solid tumor neoplastic meningitis. Cancer 2003; 97(12): 3053–60PubMedCrossRefGoogle Scholar
  57. 57.
    Jaeckle KA, Batchelor T, O’Day SJ, et al. An open label trial of sustained-release cytarabine (DepoCyt) for the intrathecal treatment of solid tumor neoplastic meningitis. J Neurooncol 2002; 57(3): 231–9PubMedCrossRefGoogle Scholar
  58. 58.
    Apfelbaum JL, Chen C, Mehta SS, et al. Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg 2003; 97(2): 534–40PubMedCrossRefGoogle Scholar
  59. 59.
    Svensson I, Sjostrom B, Haljamae H. Assessment of pain experiences after elective surgery. J Pain Symptom Manage 2000; 20(3): 193–201PubMedCrossRefGoogle Scholar
  60. 60.
    Shea RA, Brooks JA, Dayhoff NE, et al. Pain intensity and postoperative pulmonary complications among the elderly after abdominal surgery. Heart Lung 2002; 31(6): 440–9PubMedCrossRefGoogle Scholar
  61. 61.
    Tsui SL, Law S, Fok M, et al. Postoperative analgesia reduces mortality and morbidity after esophagectomy. Am J Surg 1997; 173(6): 472–8PubMedCrossRefGoogle Scholar
  62. 62.
    Pavlin DJ, Chen C, Penaloza DA, et al. Pain as a factor complicating recovery and discharge after ambulatory surgery. Anesth Analg 2002; 95(3): 627–34PubMedGoogle Scholar
  63. 63.
    Perkins FM, Kehlet H. Chronic pain as an outcome of surgery: a review of predictive factors. Anesthesiology 2000; 93(4): 1123–33PubMedCrossRefGoogle Scholar
  64. 64.
    Quality improvement guidelines for the treatment of acute pain and cancer pain. American Pain Society Quality of Care Committee. JAMA 1995; 274(23): 1874–80CrossRefGoogle Scholar
  65. 65.
    Agency for Health Care Policy and Research. Acute pain management: operative or medical procedures and trauma. Clinical Practice Guideline. Rockville (MD): Agency for Health Care Policy and Research, 1992Google Scholar
  66. 66.
    Richman JM, Wu CL. Epidural analgesia for postoperative pain. Anesthesiol Clin North America 2005; 23(1): 125–40PubMedCrossRefGoogle Scholar
  67. 67.
    Jain S, Datta S. Postoperative pain management. Chest Surg Clin N Am 1997; 7(4): 773–99PubMedGoogle Scholar
  68. 68.
    Sinatra RS, Torres J, Bustos AM. Pain management after major orthopaedic surgery: current strategies and new concepts. J Am Acad Orthop Surg 2002; 10(2): 117–29PubMedGoogle Scholar
  69. 69.
    Block BM, Liu SS, Rowlingson AJ, et al. Efficacy of postoperative epidural analgesia: a meta-analysis. JAMA 2003; 290(18): 2455–63PubMedCrossRefGoogle Scholar
  70. 70.
    Rawal N, Sjostrand U, Dahlstrom B. Postoperative pain relief by epidural morphine. Anesth Analg 1981; 60(10): 726–31PubMedCrossRefGoogle Scholar
  71. 71.
    Fuller JG, McMorland GH, Douglas MJ, et al. Epidural morphine for analgesia after caesarean section: a report of 4880 patients. Can J Anaesth 1990; 37(6): 636–40PubMedCrossRefGoogle Scholar
  72. 72.
    Rauck RL, Raj PP, Knarr DC, et al. Comparison of the efficacy of epidural morphine given by intermittent injection or continuous infusion for the management of postoperative pain. Reg Anesth 1994; 19(5): 316–24PubMedGoogle Scholar
  73. 73.
    Pastor MC, Sanchez MJ, Casas MA, et al. Thoracic epidural analgesia in coronary artery bypass graft surgery: seven years’ experience. J Cardiothorac Vasc Anesth 2003; 17(2): 154–9PubMedCrossRefGoogle Scholar
  74. 74.
    Flisberg P, Rudin A, Linner R, et al. Pain relief and safety after major surgery: a prospective study of epidural and intravenous analgesia in 2696 patients. Acta Anaesthesiol Scand 2003; 47(4): 457–65PubMedCrossRefGoogle Scholar
  75. 75.
    Pan PH, Bogard TD, Owen MD. Incidence and characteristics of failures in obstetric neuraxial analgesia and anesthesia: a retrospective analysis of 19,259 deliveries. Int J Obstet Anesth 2004; 13(4): 227–33PubMedCrossRefGoogle Scholar
  76. 76.
    Horlocker TT, Wedel DJ, Benzon H, et al. Regional anesthesia in the anticoagulated patient: defining the risks (the second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation). Reg Anesth Pain Med 2003; 28(3): 172–97PubMedGoogle Scholar
  77. 77.
    Brooks K, Pasero C, Hubbard L, et al. The risk of infection associated with epidural analgesia. Infect Control Hosp Epidemiol 1995; 16(12): 725–8PubMedCrossRefGoogle Scholar
  78. 78.
    Kim T, Kim J, Kim S. Extended-release formulation of morphine for subcutaneous administration. Cancer Chemother Pharmacol 1993; 33(3): 187–90PubMedCrossRefGoogle Scholar
  79. 79.
    Kim T, Murdande S, Gruber A, et al. Sustained-release morphine for epidural analgesia in rats. Anesthesiology 1996; 85(2): 331–8PubMedCrossRefGoogle Scholar
  80. 80.
    Yaksh TL, Provencher JC, Rathbun ML, et al. Pharmacokinetics and efficacy of epidurally delivered sustained-release encapsulated morphine in dogs. Anesthesiology 1999; 90(5): 1402–12PubMedCrossRefGoogle Scholar
  81. 81.
    Yaksh TL, Provencher JC, Rathbun ML, et al. Safety assessment of encapsulated morphine delivered epidurally in a sustained-release multivesicular liposome preparation in dogs. Drug Deliv 2000; 7(1): 27–36PubMedCrossRefGoogle Scholar
  82. 82.
    Viscusi ER, Martin G, Hartrick CT, et al. Forty-eight hours of postoperative pain relief after total hip arthroplasty with a novel, extended-release epidural morphine formulation. Anesthesiology 2005; 102(5): 1014–22PubMedCrossRefGoogle Scholar
  83. 83.
    Carvalho B, Riley E, Cohen SE, et al. Single-dose, sustainedrelease epidural morphine in the management of postoperative pain after elective cesarean delivery: results of a multicenter randomized controlled study. Anesth Analg 2005; 100(4): 1150–8PubMedCrossRefGoogle Scholar
  84. 84.
    Hartrick CT, Martin G, Kantor G, et al. Evaluation of a singledose, extended-release epidural morphine formulation for pain after knee arthroplasty. J Bone Joint Surg Am 2006; 88(2): 273–81PubMedCrossRefGoogle Scholar
  85. 85.
    Viscusi ER, Kopacz D, Hartrick C, et al. Single-dose extendedrelease epidural morphine pharmacokinetics. Am J Ther 2006; 13(5): 423–31PubMedCrossRefGoogle Scholar
  86. 86.
    Gould EM, Manvelian G. A pooled analysis of extended-release epidural morhphine pharmacokinetics [abstract no. A770]. Anesthesiology 2005; 103: 28Google Scholar
  87. 87.
    American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology 2004; 100(6): 1573–81CrossRefGoogle Scholar
  88. 88.
    Contopoulos-Ioannidis DG, Giotis ND, Baliatsa DV, et al. Extended-interval aminoglycoside administration for children: a meta-analysis. Pediatrics 2004; 114(1): e111–8PubMedCrossRefGoogle Scholar
  89. 89.
    Barza M, Ioannidis JP, Cappelleri JC, et al. Single or multiple daily doses of aminoglycosides: a meta-analysis. BMJ 1996; 312(7027): 338–45PubMedCrossRefGoogle Scholar
  90. 90.
    Ali MZ, Goetz MB. A meta-analysis of the relative efficacy and toxicity of single daily dosing versus multiple daily dosing of aminoglycosides. Clin Infect Dis 1997; 24(5): 796–809PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  1. 1.Department of AnesthesiaStanford University School of MedicineStanfordUSA

Personalised recommendations