Influence of ion-pair formation on the pharmacokinetic properties of drugs. Pharmacokinetic interactions of bretylium and hexylsalicylic acid in rabbits.

The simultaneous i.v. administration of equimolar doses of bretylium and hexylsalicylic acid results in an increase in plasma area under the curve value of both substances in comparison with their separate administration. The higher plasma levels of both compounds were associated with a reduced renal excretion and an increased biliary elimination. However, the increase in biliary excretion did not compensate for the reduced elimination of bretylium and hexylsalicylic acid via the kidney. The results presented in this paper give further evidence that ion-pairing in-vivo may result in altered pharmacokinetics of drugs particularly due to changes in biliary or renal excretion.

[Nephrotoxicity and myelotoxicity of antineoplastic Pt(II) and Pt(IV) coordination compounds in rats]. / Nephrotoxizität und Myelotoxizität antineoplastisch wirksamer Pt(II)- und Pt(IV)-Koordinationsverbindungen bei Ratten.

In comparison with cis-DDP four new platinum (II) and platinum (IV) complexes were evaluated for their acute nephrotoxic and myelotoxic potency in male rats following i.v. administration of maximum tolerated doses on 5 consecutive days. Parameters for nephrotoxicity determined on day 6, 13 and 22 after the first administration of the drugs included blood, urea nitrogen, serum creatinine, urine volume, urinary glucose and tubule cell excretion. Parameters for myelotoxicity determined on the same days included leucocytes, platelets, hemoglobin and hematocrit. Cis-DDP was found to be the most nephrotoxic compound. The myelotoxicity of the new platinum complexes appeared to be similar to that of cis-DDP with exception of trans-ODDP.

[Acute and subacute toxicity of antineoplastic Pt(II) and Pt(IV) coordination compounds in laboratory rodents]. / Akute und subakute Toxizität antineoplastisch wirksamer Pt(II)- und Pt(IV)-Koordinationsverbindungen bei Labornagern.

After single i.v. administration of cis-diammine-platinum(II)-lactate cis-diammine-platinum(II)-lactate, L cis-diammine-platinum(II)-dilactate trans-dihydroxy-cis-dichlorodiammine-platinum(IV), the LD50 values have been calculated to range between 80 and 130 mg/kg in mice, and between 22 and 45 mg/kg in rats. The LD50 of cis-DDP amounted to 17 mg/kg and 6.6 mg/kg, respectively. Likewise, the compounds have been found to be about 3 to 5 times less toxic than the standard cis-DDP when administered daily for 5 consecutive days. Since the kidneys, the bone marrow, the lymphatic tissue and the intestinal tract have been proved to be the main target organs, the profile of the toxic action of the Pt(II)-complexes seems to be similar to that of cis-DDP. Additionally, the Pt(IV) compound has been found to be toxic to the pancreas, the liver and the salivary glands. With regard to the antineoplastic activity the more soluble lactates of cis-DDP showed a smaller therapeutic index compared to cis-DDP.

[Pharmacological and toxicological study of turimycin]. / Pharmakologisch-toxikologische Untersuchung von Turimycin.

Turimycin is characterised by low acute toxicity. Mean lethal doses for mouse and rat are 750 mg/kg body weight for intraperitoneal application of something in excess of 3,000 mg/kg for oral administration. The blood pressure of anaesthetised cats may be reduced by amounts depending on intravenous Turimycin doses (between 10 and 50 mg/kg). The hypotensive effect of Turimycin is attributable to its negative inotropic effect on the heart and its spasmolytic action on the unstriated muscles. Reversible reduction of urine and ion excretion of rat following intraperitoneal application of 50 mg/kg body weight of Turimycin is interpreted as a consequence of such action upon blood pressure. A preliminary study was conducted into dogs which had orally received daily Turimycin doses of 50 or 125 mg/kg body weight over twelve months. No substance-depending functional or morphological damage was recorded.