Pharmacokinetics of vindesine bolus and infusion

Jackson, Don V.; Sethi, V. Sagar; Long, Tony; Muss, Hyman B.; Spurr, Charles L.

doi:10.1007/bf00257126

Cited by 12 publications

(5 citation statements)

References 13 publications

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“…Therefore, t ½U represents a more realistic estimation of vincristine elimination half‐life after VSLI administration. The t ½U (45 hours) fell within the range of terminal elimination half‐lives reported for vincristine, 5.1 ± 3.5 to 85 ± 69 hours, 8,9 with most studies reporting a half‐life of about 22 hours 7,17,31,32 . More recent studies using HPLC methods, rather than radioimmunoassay methods, to quantitate plasma vincristine reported terminal elimination half‐lives of 19.4 ± 3.6 hours and 31 ± 17 hours for vincristine 10,16 .…”

Section: Discussionmentioning

confidence: 61%

Pharmacokinetics and Urinary Excretion of Vincristine Sulfate Liposomes Injection in Metastatic Melanoma Patients

Bedikian

Vardeleon

Smith

et al. 2006

The Journal of Clinical Pharma

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Vincristine sulfate liposomes injection (VSLI) is a liposomal formulation of vincristine encapsulated in sphingosomes composed of sphinogomyelin and cholesterol (58/42; mol/mol). The pharmacokinetics and urinary excretion of VSLI were evaluated in 12 patients with metastatic melanoma after single-dose (2.0 mg/m2 every 2 weeks = 1 cycle) and multiple-dose (cycle 3, pharmacokinetics only) administrations (intravenous infusion over 1 hour). After VSLI infusion, total (released and encapsulated) vincristine concentrations in plasma remained relatively constant for 3 to 12 hours and thereafter declined, with interpatient variability seen in the rate of decline resulting in monoexponential or biexponential profiles. The area under the plasma concentration-time curve from time zero to infinity of total vincristine in plasma ranged from 4933 to 40495 h.ng/mL and total clearance ranged from 131 to 445 mL/h. The volume of distribution at steady state was 2650 +/- 731 mL, indicating VSLI was mainly confined within the plasma. The released vincristine concentrations in plasma were below the level of quantitation in 95% of samples. The pharmacokinetic parameters were similar between cycles 1 and 3, and trough plasma levels of total vincristine were below the level of quantitation of 1 ng/mL. Approximately 8% of the injected dose was excreted in the urine as unchanged vincristine (7%) or N-desformylvincristine (0.8%). Overall, VSLI exhibited a longer circulation half-life and higher area under the plasma concentration-time curve compared to conventional vincristine, whereas its route of elimination remained unchanged.

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Section: Discussionmentioning

confidence: 61%

Pharmacokinetics and Urinary Excretion of Vincristine Sulfate Liposomes Injection in Metastatic Melanoma Patients

Bedikian

Vardeleon

Smith

et al. 2006

The Journal of Clinical Pharma

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“…The in vitro cyotoxic activity of taxol and vindesine was very high (IC 50 values in the nanomolar range), mainly below the peak concentrations obtainable in the plasma with clinical administration of these drugs [23,19].…”

Section: Discussionmentioning

confidence: 94%

“…The drug concentrations tested were in the range of those achievable in the plasma following administration of the usual therapeutic drug doses [19][20][21][22][23]. At the end of treatment cells were fixed with trichloroacetic acid (50% aqueous solution) at 48C for 1 h, air-dried and stained for 30 min with sulphorodamine B (SRB) 0.4% in 1% acetic acid at room temperature.…”

Section: Cell Growth Inhibition Studiesmentioning

confidence: 99%

Immunophenotypical markers, ultrastructure and chemosensitivity profile of metastatic melanoma cells

et al. 2002

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The survival of patients affected by cutaneous melanoma has improved dramatically in the last 10 years, because of earlier diagnosis. Despite this, the therapeutic results obtained in metastatic melanoma (MM) are very disappointing due to its poor responsiveness to cytotoxic agents. In this type of solid tumor, tumor chemosensitivity assays have been suggested to be an important tool to predict clinical responsiveness to therapy. Metastatic melanoma cells (MMCs) were obtained from subcutaneous melanoma metastases of five patients and cultured for several consecutive passages. An immunofluorescence and an electron microscopic study were performed in order to establish the ultrastructural and physiopathological features of MMCs. A sulphorodamine-B test was used to measure in vitro sensitivity of MMCs to temozolomide, cisplatin, vindesine, taxol and interpheron alpha-2a. Following a 72 h exposure, maximum activity was obtained with vindesine (median inhibitory concentration, IC 50 , 0.23 nM) and taxol (median IC 50 0.31 nM). Cisplatin median IC 50 values were higher (4.6 mM) than taxol and vindesine, but still in the range of clinically achievable plasma concentrations. Temozolomide inhibited cell proliferation only at very high concentrations (median IC 50 228 mM). No significant cell growth inhibitory effects (#25%) were observed with interferon alpha-2a concentrations up to 8000 IU/ml. MMCs expressed progression markers typical of cutaneous metastatic melanoma and showed poor sensitivity in vitro to most anticancer drugs tested, including temozolomide. q

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“…In a pharmacokinetic analysis of a 5 day infusion regimen (Jackson et al, 1984b) there was also no accumulation of the drug found. The area under the curve (AUC) calculated for a patient with a hypothetical steady state plasma level of 0.8 ng ml-(the highest level detected in one of our patients) is still smaller than the AUC in the 2 day infusion (total dose 5.4mg) or bolus injection (total dose 4.0-5.0mg) found by others (Jackson et al, 1984b;Rahmani et al, 1985). In the study of Jackson et al (1984b) only mild neurotoxicity was seen.…”

mentioning

confidence: 94%

“…Responses were seen with continuous infusion in tumours resistant to bolus injections of vinca alkaloids (Mathe et al, 1978;Mascret et al, 1983). The rationale for such schedules has been based on the relatively short plasma half-life of VDS in pharmacological studies (Jackson et al, 1984b), and the fact that vinca alkaloids are cell cycle specific drugs. We performed a study of a 21-day continuous infusion of VDS administered with an ambulatory pump.…”

mentioning

confidence: 99%