ABSTRACT
The pharmacokinetics and toxicity of (-)-(S)-bromofosfamide ((2S)-(2-chloroethylamino)-3-(2-bromoethyl)-1,3,2-oxazaphosphorinae 2-oxide, CAS 146452-37-1, CBM-11) were determined in ten patients with non-small cell lung cancer following an oral dose of 1.38 g/m2 B.S.A. (Body Surface Area). The drug was given as a powder in gelatine capsules to fasting patients. Plasma samples were collected during the first 24 h after administration. All samples, after extraction with chloroform, were assayed by a reverse phase HPLC method using UV detection at 200 nm. Orally administered (-)-(S)-bromofosfamide showed relatively fast absorption kinetics. Peak concentration of 47 micrograms/ml was observed after 1 h. The average half-life was about 5 h. Toxicities associated with oral (-)-(S)-bromofosfamide therapy consisted of symptoms regarding the central nervous system, gastrointestinal tract and urinary tract. Neurotoxic symptoms were the most common clinically significant side effects and probably dose limiting.
Subject(s)
Antineoplastic Agents, Alkylating/adverse effects , Antineoplastic Agents, Alkylating/pharmacokinetics , Carcinoma, Non-Small-Cell Lung/metabolism , Ifosfamide/adverse effects , Ifosfamide/pharmacokinetics , Lung Neoplasms/metabolism , Administration, Oral , Aged , Area Under Curve , Blood Cell Count , Bone Marrow Diseases/chemically induced , Bone Marrow Diseases/pathology , Chromatography, High Pressure Liquid , Female , Half-Life , Humans , Ifosfamide/analogs & derivatives , Male , Middle Aged , Spectrophotometry, UltravioletABSTRACT
(-)-(S)-Bromofosfamide ((2S)-(2-chloroethylamino)-3-(2-bromoethyl)-1,3,2-oxazaphosphorinane 2-oxide, CAS 146452-37-1, CBM-11) is a new potential anti-cancer drug, currently under investigation. Its pharmacokinetics and bioavailability were studied in female mice following intravenous and oral administration of the dose of 50 mg/kg. The compound was extracted from plasma samples using chloroform and analyzed by high-performance liquid chromatography with UV detection at 200 nm. Orally administered (-)-(S)-bromofosfamide was absorbed quickly, attaining a maximum level of 33.9 micrograms/ml at 5 min, and was eliminated with a half-life (t1/2) of about 0.9 h. The average half-life of intravenously administered (-)-(S)-bromofosfamide was about 0.7 h. The total plasma clearance (CL) and volume of distribution (Vd) were found to be 0.14 l/h and 4.92 l/kg, respectively. The absolute bioavailability of (-)-(S)-bromofosfamide after oral administration was 105%.
Subject(s)
Antineoplastic Agents, Alkylating/pharmacokinetics , Ifosfamide/pharmacokinetics , Administration, Oral , Animals , Antineoplastic Agents, Alkylating/administration & dosage , Area Under Curve , Biological Availability , Chromatography, High Pressure Liquid , Female , Half-Life , Ifosfamide/administration & dosage , Ifosfamide/analogs & derivatives , Injections, Intravenous , Mice , Spectrophotometry, UltravioletABSTRACT
In this open, randomized, two way crossover, bioequivalence study, two 5 mg tablet preparations of glipizide (Glipizyd tabl. 5 mg, Tarchominskie Zaklady Farmaceutyczne POLFA S.A., and Glibenese tabl. 5 mg, Pfizer), were compared in 24 healthy male volunteers. Pharmacokinetic variables (mean maximum plasma concentration, mean time to reach maximum plasma concentration, and the mean area under the plasma concentration-time curve) were not statistically significantly different for the two formulations. It can be concluded that the two tablet preparations of glipizide are likely to be bioequivalent.
Subject(s)
Glipizide/pharmacokinetics , Hypoglycemic Agents/pharmacokinetics , Adult , Area Under Curve , Chromatography, High Pressure Liquid , Glipizide/administration & dosage , Glipizide/analysis , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/analysis , Male , Reproducibility of Results , Tablets , Therapeutic EquivalencyABSTRACT
A high-performance liquid chromatographic method for the determination of miconazole in human plasma is described. A solid-phase extraction was performed on an octadecyl (C18) cartridge. Miconazole was eluted with methanol, separated on a reversed-phase column and was measured by ultraviolet detection at 230 nm. The absolute extraction recovery from plasma samples was 85%. The limit of detection was established as 5 ng/ml. The coefficient of variation of the determination of plasma levels by this method over the standard curve concentration range was less than 10%, except with the concentration of 10 ng/ml. The plasma levels of miconazole in twelve healthy volunteers given a 250-mg oral dose of two tablet forms were determined by this method.