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PubMed1987

[Intraperitoneal versus intravenous infusion of cis-platinum in advanced ovarian cancer--examination of pharmacokinetics].

The pharmacokinetics of i.p.- and i.v.-infused cis-platinum (55 mg/m2) was studied in five patients with advanced ovarian cancer. The area under the concentration time (AUC) of non-protein-binding platinum in ascites had on anti-tumor activity 44 times larger with i.p. infusion than that with i.v. infusion. Comparing with the concentration curve of non-protein-binding platinum in plasma, there was little difference between i.p. and i.v. infusion, and the AUC of non-protein-binding platinum was almost equal between i.p. and i.v. infusion. In cases of low renal function, cisplatin was infused at 70 mg/m2 with sodium thiosulfate (STS). The AUC of ultrafiltrable platinum in plasma was 3 times larger in STS combination therapy. Therefore, STS was confirmed to be a powerful antidote against cis-platinum in plasma. Amounts of total platinum in 24-h urinary secretion were slightly less for i.p. than for i.v. infusion. Consequently, i.p. infusion of cis-platinum was shown to be highly effective on the local site and as effective as i.v. infusion on the whole body. Moreover, this route is effective for reducing ascites production and is expected to be effective against metastatic sites other than the abdominal cavity.

Adolescent↗
PubMed1988

Dose-dependent down-regulation of beta-adrenergic receptors after chronic intravenous infusion of antidepressants.

1. The effects of intravenous infusion of desipramine (1, 3, 10, and 60 mg/kg/day), amitriptyline, zimelidine, iprindole (3, 10, 30, 60, and 100 mg/kg/day each), imipramine (10, 30, and 100 mg/kg/day), or U-48753E (1, 3, 10, and 30 mg/kg/day) on the density of central beta-adrenergic receptors (beta-AR) were investigated in female Sprague-Dawley rats. 2. Desipramine, amitriptyline, zimelidine, iprindole, imipramine, and U-48753E dose-dependently reduced the density of beta-AR in the cerebral cortex. 3. The time of onset of down-regulation of beta-AR was negatively correlated with the doses of drugs. 4. At equipotent doses, antidepressants seem to have a similar profile for the time of onset of reduction in the density of beta-AR. 5. The results indicate that down-regulation of beta-AR may be involved in mediating the therapeutic effects of antidepressants, and this effect can be rapidly achieved by intravenous infusion of drugs.

Amitriptyline↗