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Biomedical subjects

D C Chatterji

Publications and source records attributed to D C Chatterji.

At least 19 recordsLinked to original sources
PubMed1985

Reduced systemic drug exposure by combining intra-arterial chemotherapy with hemoperfusion of regional venous drainage.

Four patients with malignant cerebral gliomas received 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) into the internal carotid artery (ICA) while the ipsilateral jugular drainage was pumped extracorporeally through a hemoperfusion cartridge containing a nonionic adsorbant resin. Each patient received 220 mg/sq m BCNU, infused over 45 minutes through a toposcopic catheter positioned with the tip in the ICA beyond the origin of the ophthalmic artery. Jugular blood was pumped extracorporeally at 300 ml/min through a large-bore catheter in the jugular bulb. Plasma samples were obtained for BCNU measurement at frequent intervals from the right atrium. During a separate treatment, 6 weeks before or after the hemoperfusion treatment, the same dose of BCNU was infused into the ICA and atrial samples were obtained on a similar schedule. Hemoperfusion of the jugular blood during intracarotid infusion reduced the systemic exposure by 56% to 87% and increased total body clearance of BCNU by two- to eightfold. The calculated pharmacokinetic advantage (brain:body exposure ratio) was between 21 and 55:1 when the combined treatment was used.

Adolescent↗
PubMed1985

Arterial drug infusion with extracorporeal removal. II. Internal carotid carmustine in the rhesus monkey.

During cancer chemotherapy by intra-arterial drug administration, systemic toxicity often limits the tolerable dose. We evaluated the pharmacokinetic advantage obtained by infusing carmustine (BCNU) into the internal carotid artery during BCNU removal from the blood from the perfused region by hemoperfusion. A hemoperfusion column (XR-010, Extracorporeal Medical Specialties) was shown to remove BCNU quantitatively from sheep blood flowing at 300 ml/minute when the drug was infused at 13 mg/minute for 30 minutes. Under general anesthesia, adult rhesus monkeys underwent catheterization of the internal carotid artery and placement of a catheter in the ipsilateral jugular vein at its junction with the sigmoid sinus. BCNU (10 mg/kg) was infused over 20 minutes while blood was pumped from the jugular vein through a small column and back into the inferior vena cava. The procedure reduced systemic exposure by 46%-84% compared with iv infusion of the same dose. Brain-to-systemic exposure ratios ranged from 18:1 to 87:1, depending on the pump flow rate and method of calculation. Hematopoietic toxicity was prevented. It is suggested that tumor exposure to BCNU comparable to that associated with very high tumor cell kill in vitro may be feasible with little or no systemic toxicity.

Animals↗
PubMed1984

Quantitation of flupirtine and its active acetylated metabolite by reversed-phase high-performance liquid chromatography using fluorometric detection.

A simple, selective and sensitive procedure is described for the quantitation of flupirtine maleate (FLU) and its active acetylated metabolite (Met. 1) in plasma and urine. Using a 0.5-ml sample, a sensitivity of 10 ng/ml is easily achieved with a reversed-phase octadecylsilane (C18) column, and a high-performance liquid chromatographic system with fluorescence detection. Quantitation from plasma involves addition of an internal standard, protein precipitation with acetonitrile and a sample concentrating step, while for urinalysis the samples are taken through a single extraction with methylene chloride. Analytical recoveries of FLU and Met. 1 from plasma averaged greater than or equal to 95%, while from urine only 60 and 50%, respectively, could be recovered. The overall, inter- and intra-day variability for both FLU and Met. 1 averaged 6, 5 and 3%, in plasma, respectively. Standard calibration plots in plasma were linear (r greater than or equal to 0.99) for FLU (range: 0.01-10.0 micrograms/ml) and Met. 1 (range: 0.5-25 micrograms/ml) over the extended range. A slightly modified elution system was employed for quantitation of FLU and Met. 1 in urine.

Acetylation↗
PubMed1984

Long-term stability of aqueous solutions of luteinizing hormone-releasing hormone assessed by an in vitro bioassay and liquid chromatography.

The stability of aqueous solutions of luteinizing hormone-releasing hormone (LHRH) after extended storage at various temperatures was investigated using a newly developed HPLC assay and an in vitro dispersed pituitary cell culture bioassay. Good correlations were obtained between the potency obtained by HPLC and bioassay in samples stored at 37 degrees C or subjected to different stress conditions. No significant decrease in activity of LHRH was observed in aqueous solutions stored at 37 degrees C for up to 10 weeks, at 4 degrees C for 2 years, or subjected to repeated freezing and thawing for 5 d. Heating to 60 degrees C in sterile pH 9.0 buffer up to 11 d and storage at ambient temperature in nonsterile solution for 4 months produced well-distinguished degradation products and a decrease in potency. It is concluded that sterile aqueous solutions of LHRH are stable for at least 10 weeks at 37 degrees C and, thus, could be reliably used for chronic administration when long-term stability at body temperature is important.

Animals↗
PubMed1983

Quantitation of testolactone and 4,5-dihydrotestolactone in plasma and urine using high-performance liquid chromatography.

A rapid, sensitive, and selective assay is described for the quantitation of both testolactone and its recently identified metabolite, 4,5-dihydrotestolactone, in plasma and urine using high-performance liquid chromatography. The procedure includes a methylene chloride extraction prior to chromatography and quantitation using peak height ratios (ultraviolet absorbance detection, 242 nm) of testolactone and 4,5-dihydrotestolactone to the internal standard, testosterone. A sensitivity of 20 ng/ml for both testolactone and 4,5-dihydrotestolactone is easily achieved using only 0.5 ml of sample. Mean recoveries for testolactone and its metabolite are 95.0% and 81.8%, respectively, and the mean coefficient of variation of the procedure is 3.5% for the drug and 7.1% for the metabolite. This method is currently being used to study the pharmacokinetics of testolactone and 4,5-dihydrotestolactone in male patients. A steady-state plasma concentration versus time profile from a representative patient is included.

Chromatography, High Pressure Liquid↗
PubMed1983

Carbamazepine and its -10,11-epoxide metabolite in plasma and CSF. Relationship to antidepressant response.

Levels of carbamazepine and its -10,11-epoxide metabolite were measured in plasma and CSF of affectively ill patients treated only with carbamazepine for an average of 33 days at an average dosage of 1,055 mg/day. The CSF levels of carbamazepine were 2.06 micrograms/mL (ie, 31% of plasma levels, which equaled 6.55 micrograms/mL); CSF -10,11-epoxide concentrations averaged 0.91 micrograms/mL in 18 subjects (63% of those found in plasma). Carbamazepine levels in plasma or CSF were not related to degree of antidepressant or antimanic response. In contrast, concentrations of the -10,11-epoxide metabolite were correlated with the degree of antidepressant response. This preliminary study suggests the possibility that the -10,11-epoxide metabolite of carbamazepine may be related to the degree of clinical efficacy in affectively ill patients and may thus possess active psychotropic properties in man in addition to its reported anticonvulsant effects in animals.

Adult↗
PubMed1983

Quantitation of ketoconazole in biological fluids using high-performance liquid chromatography.

A rapid, specific procedure is described for the quantitation of ketoconazole in biological fluids using high-performance liquid chromatography (HPLC). The procedure involves sample preparation using a reverse-phase C-18 cartridge prior to chromatography and quantitation using peak height ratios (UV absorbance detection, 231 nm) of ketoconazole to the internal standard, phenothiazine. A sensitivity of 0.2 micrograms/ml was achieved using a 0.5-ml sample. The mean recovery was 86.2%, and overall coefficient of variation of the procedure was 7.1%. This procedure has been used to determine ketoconazole levels in human serum, plasma, CSF, and synovial fluid. A comparison with a microbiological assay is presented, and adaptability of this procedure to quantitation by fluorescence to increase the sensitivity fivefold is discussed.

Biological Assay↗
PubMed1983

Rapid GC method for quantitation of nifedipine in serum using electron capture detection.

For studying the pharmacokinetics of nifedipine after single doses, a rapid, specific, reliable gas chromatographic assay procedure for nifedipine in serum is developed. Using a single-step solvent extraction or a bonded-phase column extraction and electron capture detection, an assay sensitivity of 10 to 25 ng/ml can be achieved using 0.25 ml of serum. The assay quantitates intact nifedipine and separates it reproducibly from its nitro- and nitrosopyridine derivatives.

Chromatography, Gas↗
PubMed1982

Quantitation of 6-mercaptopurine in biologic fluids using high-performance liquid chromatography: a selective and novel procedure.

A simple, selective, sensitive and rapid procedure is described for the quantitation of 6-mercaptopurine (6-MP) in biological fluids. A sensitivity of at least 5 ng/ml is easily achieved in plasma on a reversed-phase octadecylsilane (C18) column using a high-performance liquid chromatography system following an initial protein precipitation and a clean-up step. Mean extractability of the drug from plasma following this procedure is greater than 98% and the overall coefficient of variation for the assay is below 6%. Plasma levels of 6-MP were measured in a rhesus monkey for 12 h following an intravenous administration of a single bolus dose (4 mg/kg) of 6-MP.

Animals↗
PubMed1982

Kinetics of chlorambucil hydrolysis using high-pressure liquid chromatography.

A stability-specific high-pressure liquid chromatographic (HPLC) method was developed to assay intact chlorambucil (I) in the presence of its hydrolytic decomposition products. The HPLC method was used to follow the degradation kinetics of I over pH 1.0-10.0 in the presence of various buffers with and without added chloride ion. In the absence of chloride ion, the hydrolysis of I followed first-order kinetics and the pH rate profile showed a sharp inflection around pH 2.5 attributable to the ionization of the nitrogen mustard and a shallower inflection around pH 5.0 attributable to the ionization of the carboxylic group. The rate was pH independent over pH 6.0-10.0 and independent of buffer species in the absence of chloride ion. IN the presence of chloride ion, the kinetics of I hydrolysis was still first order. However, the degradation half-life at a particular pH and buffer concentration increased linearly with chloride concentration. Kinetic evidence is presented to show that the mechanism of chloride stabilization involves the attack of chloride ion on the unstable cyclic ethyleneimmonium intermediate to give back I. Implications of the kinetic data obtained on the fate of orally administered I are discussed.

Chlorambucil↗
PubMed1982

Biodistribution study of Ethiodized Oil Emulsion 13 for computed tomography of the liver and spleen.

Biodistribution studies were conducted with a new intravenous lipoid contrast material currently undergoing clinical trials in four hospitals. The contrast material selectively opacifies the liver and spleen for computed tomographic examination. The experiments were performed on rats with 125I-labeled ethiodized oil emulsion. The study showed that the liver accumulates nearly 80% of the injected iodine within 15 min of the injection and retains a high concentration over 3 h. The second highest concentration was found in the spleen. More than 99% of the iodine is eliminated from the liver and spleen within 48 h, primarily through the kidneys.

Animals↗
PubMed1982

Computed tomography of the liver and spleen with intravenous lipoid contrast material: review of 60 examinations.

In 60 computed tomographic examinations of the liver and spleen in 55 patients, a new intravenous lipoid contrast material, Ethiodized Oil Emulsion 13, was used. This organ-specific contrast material, retained by the reticuloendothelial cells of the liver and spleen, caused marked increase in the attenuation of the liver and spleen, but did not appreciably change the attenuation of the tumor involving these organs, thereby significantly increasing the density differential between normal and abnormal tissue. Toxicity was considered to be well within tolerable limits with the most frequently noted untoward side effects of chills, fever, headaches, and foul metallic taste. Ethiodized Oil Emulsion 13 holds the promise to become a valuable clinical tool by which hepatic and splenic imaging may be significantly improved and lesions less than 1 cm in diameter demonstrated in the liver and spleen.

Adult↗
PubMed1980

Clinical trials with a new intravenous liposoluble contrast material for computed tomography of the liver and spleen.

Ten patients with disseminated cancer were given intravenous injections of 0.2 ml/kg (40 mg l/kg) of the experimental contrast material EOE 13. Ct scans of the liver and spleen were taken prior to and 30 minutes after contrast infusion. Visualization of the liver was significantly improved in 5, moderately improved in 3, and not appreciably improved in 2. The spleen showed an obvious increase in density in all cases. No significant toxicity was encountered: untoward side effects consisted of fever, headaches, foul metallic taste, and weakness for a short period. Four patients had no side effects, and 2 experienced only abnormal taste sensation. Further experimental and clinical work is needed before the advantages and safety of this contrast material can be documented.

Autopsy↗