Experiment 960145
Compounds isolated
Details
| Property | Value |
|---|---|
| Pharmacology | |
| Administration route | IV INFUSION |
| Organism | Empty organism |
| Citation | GENELABS: SANDOZ:. (1991). COMPOUND Q TRISCHOSANTHIN GLQ223.. 16(6) |
| Amount utilized | |
| Compound isolated | |
| Disease | A PHASE I DOSE-ESCALATING STUDY WAS CARRIED OUT IN ORDER TO EVALUATE THE SAFETY AND PHARMACOKINETICS OF SINGLE IV INFUSIONS OF THE TITLE COMPOUND IN 18 PATIENTS WITH AIDS OR ARC. NO NOTICEABLE TOXICITIES WERE SEEN, EXCEPT FOR A SEVERE NEUROLOGICAL ADVERSE REACTION IN ONE PATIENT. NO CONSISTANT OR SUSTAINED ALTERATIONS IN HIV ANTIGEN LEVELS OR CD4+ LYMPHOCYTE POPULATIONS WERE NOTED. SERUM CONCENTRATIONS APPROXIMATING THOSE EFFECTIVE IN IN VITRO STUDIES WERE REACHED TRANSIENTLY, BUT WERE NOT MAINTAINED LONG ENOUGH TO ACHIEVE ANTIRETROVIRAL EFFECTS. FURTHER STUDIES HAVE BEEN SUGGESTED IN ORDER TO DETERMINE PHARMACODYNAMICS, OPTIMUM DOSING SCHEDULES AND EFFICACY OF THE TITLE COMPOUND AND RELATED MOLECULES IN THE TREATMENT OF HIV INFECTION. FIFTY-ONE PATIENTS WITH ADVANCED HIV DISEASE WERE ENROLLED IN A PHASE I/II DOSE-ESCALATION STUDY WITH THE TITLE COMPOUND. THREE INJECTIONS WERE GIVEN OVER A PERIOD OF 9-21 DAYS AT DOSES OF 10-30 MCG/KG/INJECTION. THE MAXIMUM TOLERATED DOSE APPEARED TO BE 30 MCG/KG. THE MAJOR DOSE-LIMITING SIDE EFFECTS WERE REVERSIBLE BUT SEVER FATIGUE AND MYALGIAS, MILD AND REVERSIBLE LEUKOCYTOSIS AND ELEVATED SERUM TRANSAMINASES WERE ALSO OBSERVED. SIX PATIENTS HAD REVERSIBLE MENTAL STATUS CHANGES RELATED TO TREATMENT BUT NOT TO DOSE; THESE WERE USUALLY MANIFESTED AS DEMENTIA BUT PROGRESSED TO COMA IN 2 PATIENTS. DEATH RESULTED IN 1 CASE. DECREASES IN SERUM P24 ANTIGEN LEVELS ONE MONTH AFTER THE FIRST INFUSION WERE SEEN IN 10/18 PATIENTS WHO ENTERED WITH ELEVATED LEVELS; ONE BECAME NEGATIVE. THESE VALUES TENDED TO REMAIN LOW THROUGHOUT THE 2 MONTH STUDY PERIOD. SIGNIFICANT DECREASES IN CD4+ CELL NUMBERS WERE SEEN IN PATIENTS WHO HAD HIGH INITIAL LEVELS AFTER ALL DOSES, BUT ONLY AFTER 3 INFUSIONS. FIFTY-ONE PATIENTS WITH ADVANCED HIV DISEASE RECEIVED 3 ESCALATED IM OR IV DOSES OF THE TITLE COMPOUND OVER 9-21 DAYS. SIGNIFICANT DECREASES IN SERUM P24 ANTIGEN LEVELS WERE NOTED ONE MONTH AFTER THE FIRST INFUSION IN 10/16 PATIENTS. ONE PATIENT CONVERTED TO NEGATIVE. OF PATIENTS RECEIVING ALL 3 INFUSIONS AND ENTERING THE STUDY WITH MORE THAN 100 CD4+ CELLS/CM, THERE WAS A SIGNIFICANT INCREASE IN CELL NUMBERS AND A DECREASE IN THE ERYTHROCYTE SEDIMENTATIO RATE. TOXICITY INCLUDED MYALGIAS, HYPOALBUMINEMIA, AND FEVER. SIX PATIENTS DEVELOPED DEMENTIA. MENTAL STATUS CHANGE WAS NOT RELATED TO DOSE, BUT TO LOW CD4+ CELLS. ONLY 1/11 TESTED PATIENTS DEVELOPED ANTIBODIES. |
| Dose amount | 10.30 MCG |
| Number | 1 |
| Qualitative result | INACTIVE |
| Animal | HUMAN ADULT |
| Per unit | KG |
| Dose expression | DOSE |