OBJECTIVESTo study the tissue distribution of nodularin in mice and the cellular location of nodularin in the target organs.

METHODSThe nodularin was labeled with radioactive isotope (125)I and then was given to mice via oral, intraperitoneal and intravenous administration. The distribution of nodularin in target organs and the cellular location of nodularin were studied by radioisotope and autoradiography techniques.

RESULTSThe radioisotope study results showed that nodularin was mainly distributed in the kidney and liver in mice. Further autoradiography study indicated that nodularin was distributed in the renal cell nuclei and liver cell nuclei.

CONCLUSIONThe kidney and liver are the two main target organs for nodularin in mice.

Animals ; Cell Nucleus ; metabolism ; Female ; Kidney ; metabolism ; Liver ; metabolism ; Male ; Marine Toxins ; pharmacokinetics ; Mice ; Peptides, Cyclic ; pharmacokinetics

Batifiban, a synthetic cyclic peptide, is a potent platelet glycoprotein GPIIb/IIIa antagonist which may be useful in the treatment and prevention of acute coronary syndromes. The pharmacokinetics and pharmacodymanic (inhibition of platelet aggregation) effects, and tolerability of batifiban were investigated in healthy subjects following single bolus injection with doses of 55, 110, or 220 microg/kg, or multiple doses of an bolus followed intravenous infusion for 24 h (180 microg/kg plus 2.0 microg/min.kg, and 220 microg/kg plus 2.5 microg/min.kg) in this phase I clinical trial. Plasma levels of batifiban and areas under the curve were found to be proportional to doses. Batifiban was rapidly eliminated with a half-life of approximately 2.5 h. Significant differences were noted for plasma levels of batifiban and areas under the curve between males and females. No significant differences in the terminal half-life were found between males and females. Batifiban reversibly inhibited ex vivo platelet aggregation in a dose- and concentration-dependent manner, consistent with its mechanism as a GPIIb/IIIa antagonist. Single and multiple intravenous doses of batifiban were found to be safe and well tolerated in healthy subjects. These results support a bolus injection plus intravenous infusion regimen of batifiban for the treatment and prevention of acute coronary syndromes.
Injections, Intravenous ; Peptides, Cyclic/*pharmacokinetics ; Peptides, Cyclic/*pharmacology ; Platelet Aggregation Inhibitors/adverse effects ; Platelet Aggregation Inhibitors/*pharmacokinetics ; Platelet Aggregation Inhibitors/*pharmacology ; Platelet Glycoprotein GPIIb-IIIa Complex/*antagonists & inhibitors ; Young Adult

The combined use of batifiban, a synthetic platelet GPII b/ IIIa receptor antagonist, and antithrombin agents is an attractive option for the treatment of patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS) and those scheduled for percutaneous coronary intervention. To observe whether antithrombin agents affect the pharmacokinetic and pharmacodynamic properties of batifiban in combination therapy and optimize clinical administration dosage of batifiban, an open-label and parallel study was conducted. Thirty healthy subjects were randomly divided into three groups, which were sequentially treated with batifiban alone, or oral coadministration of clopidogrel, aspirin and UFH, or batifiban coadministered with these antithrombin agents. Blood samples were collected at pre-specified time points. The evaluation index included the inhibition of platelet aggregation and pharmacokinetic parameters. The pharmacokinetic parameters of batifiban and batifiban coadministered with antithrombin agents showed no significant differences. The mean inhibition rate of platelet aggregation (%) suggested that neither batifiban alone nor antithrombin agents alone could provide such potent inhibition rate (>80%) to obtain the best clinical efficacy, but they had a synergistic effect on platelet inhibition. No serious adverse effects were observed. The results in these healthy subjects suggest that batifiban coadministrated with antithrombin agents could achieve optimum clinical treatment effect for patients with NSTE ACS, and also those scheduled for percutaneous coronary intervention.
Administration, Oral ; Adolescent ; Adult ; Area Under Curve ; Aspirin ; administration & dosage ; pharmacology ; China ; Drug Administration Schedule ; Female ; Fibrinolytic Agents ; administration & dosage ; pharmacology ; Heparin ; administration & dosage ; pharmacology ; Humans ; Infusions, Intravenous ; Injections, Intravenous ; Male ; Metabolic Clearance Rate ; drug effects ; Peptides, Cyclic ; administration & dosage ; pharmacokinetics ; Platelet Aggregation Inhibitors ; administration & dosage ; pharmacokinetics ; Ticlopidine ; administration & dosage ; analogs & derivatives ; pharmacology ; Time Factors ; Young Adult