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D Lamiable

Publications and source records attributed to D Lamiable.

62 records · Page 4Linked to original sources

Clinical pharmacology of gallium chloride after oral administration in lung cancer patients.

Pharmacokinetic parameters were determined in 18 lung cancer patients after a single administration of 800 mg/24 h of GaCl3: Cmax = 123 +/- 61 mu/l; Tmax = 5.2 +/- 5.5 h; AUCO-96h = 4690 +/- 3358 micrograms.l-1.h; AUCO - infinity = 6394 +/- 5352 micrograms.l-1.h; T 1/2 beta = 43 +/- 19 h. Serum Ga concentrations at the steady-state (Css) were then determined in these patients after a daily oral administration of 800 mg/24 h of GaCl3 for 15 days: Css = 274 +/- 167 micrograms/l. No correlation was found between Css and the previous pharmacokinetic parameters in each patient. Various doses of GaCl3 were administered daily to 45 patients to correlate Css and dosage. Serum Ga concentrations increased with dosage from 100 to 400 mg/24 h (p less than 0.05), but not with further dosages up to 1400 mg/24 h. The optimal daily dose of GaCl3 in lung cancer patients seems to be 400 mg/24 h. In 2 patients, Ga was assayed after death in tissues. Ga concentrations were more than 10 micrograms/g in metastases, 3.6 +/- 2.9 micrograms/g in the primary tumor and 2.3 +/- 0.9 micrograms/g in the kidney. Due to the lack of renal and hematological toxicities and the significant uptake of Ga by the tumor, GaCl3 can be used orally in conjunction with other cytotoxic agents. We intend to evaluate its efficacy according to a randomized study comparing chemotherapy versus chemotherapy plus 400 mg/24 h of GaCl3.

Administration, Oral↗

[Clomipramine and demethylclomipramine. Correlation of plasma levels and efficacy in 24 depressive patients].

Plasma concentrations of clomipramine (CL) and demethylclomipramine (DMCL) were determined in 24 patients with an endogenous (9) or non endogenous (15) depressive syndrome, treated in hospital for 21 days, with clomipramine; simultaneous clinical evaluations were performed with Hamilton Rating Scale. Optimal therapeutic effect was observed when the sum of CL + DMCL plasma levels was less 200 ng/ml or more 400 ng/ml. In our responders, the CL/DMCL ratio was around 0.6. The relation between demethylation and clinical outcome is considered.

Adult↗

Acute effects of gallium chloride on ventricular function and metabolism of the Langendorff perfused rat heart.

The effects of two concentrations of GaCl3 (1.79 microM and 7.17 microM) were studied on isolated perfused paced rat hearts. All hearts were submitted to an equilibration period of 20 minutes under normal conditions of oxygenation (95% O2, 5% CO2) and with 11 mM glucose in Krebs-Henseleit buffer. At the end of the perfusion (80 min) tissue Ga contents were 98.0 +/- 13.8 and 200.2 +/- 28.5 nM/g of wet weight for the lower and the higher Ga concentrations respectively. Left ventricular developed pressure (LVdp) as well as +LVdp/dt and -LVdp/dt were similar in control and Ga-treated groups during the 60 minutes following the equilibration period. At the same time mean coronary flow and oxygen consumption were lower (p < 0.05) in hearts perfused with 7.17 microM Ga than in the control group. Lactate production did not differ in the control and Ga-treated groups. Mean creatine kinase release was lower (p < 0.05) in the 7.17 microM Ga-treated group than in the 1.79 microM Ga-treated and control groups. Intratissular malondialdehyde as well as glycogen and ATP concentrations did not differ in all groups at the end of the experiment. Gallium chloride partially prevented the unavoidable oedema resulting from using saline Krebs-Henseleit solution. In conclusion, acute GaCl3 administration improves the functionality of the Langendorff-heart model.

Animals↗

Increased iron content in rat myocardium after 5-fluorouracil chronic administration.

The isovolumic perfused rat heart model according to Langendorff has been used in order to characterize the changes occurring in the heart following 5-Fluorouracil (5-FU) administration. Preliminary published data pointed out that perfusion of isolated heart with 1 mg/l 5-FU failed to show any differences in contractility and oxygen consumption in comparison with the control group. However, when Wistar rats received 5-FU once a day (50 mg/kg, I.P.) for five consecutive days a consistent increase in oxygen consumption throughout the 80 min of perfusion associated with a decrease in the fractional extraction of oxygen and a lowered + dP/dt max were observed, without any drug added during the in vitro perfusion. Further investigation has been performed for a better understanding of the results observed after 5-FU pretreatment. Magnesium, potassium, calcium, copper and iron contents in the myocardium (at 0 min of perfusion) were measured by flame atomic absorption spectrophotometry. Iron levels were 20% higher in the 5-FU pretreated group than in the control group, whereas as no differences were observed for the other elemental concentrations. Both initial glycogen and ATP contents were respectively 42% and 29% higher in the pretreated than in the control group and alpha-hydroxybutyrate dehydrogenase release was lower after 40 min of perfusion in the pretreated group. However, 5-FU pretreatment increased net tissue water gain after 80 min of perfusion. Increases in mean oxygen partial pressure in the myocardium and in oxygen consumption associated with increased iron level might be candidates responsible for 5-FU induced cardiotoxicity through an increased in oxygen derived free radicals. Sympathetic over-stimulation or calcium overload do not appear to be involved in 5-FU induced cardiotoxicity.

Animals↗