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Biomedical subjects

C T Bauguess

Publications and source records attributed to C T Bauguess.

11 recordsLinked to original sources
PubMed1987

The pharmacokinetics of single high doses of dexamethasone in cancer patients.

We have given single high doses of dexamethasone phosphate by intravenous infusion as an antiemetic to 15 cancer patients receiving regimens containing cisplatin and/or doxorubicin. The patients received graded doses of dexamethasone phosphate, in the range 40-200 mg, dependent upon nausea and vomiting scores, during up to three consecutive cycles of cancer chemotherapy. Plasma and urine concentrations of dexamethasone (dexamethasone alcohol) were measured by HPLC. The plasma concentration - time data were described by an open two-compartment model. The pharmacokinetic variables were independent of the dose of dexamethasone over the range studied. The terminal half-time was 4.0 +/- 0.4 h and the total body clearance was 3.5 +/- 0.4 ml X min-1 X kg-1. The volume of the central compartment and the total apparent volume of distribution were 0.23 +/- 0.03 and 1.0 +/- 0.1 l X kg-1 respectively. Approximately 8% of the dose was excreted into the urine as dexamethasone.

Aged↗
PubMed1985

Phagocytic activity of alveolar macrophages in patients with bronchogenic carcinoma.

Human bronchoalveolar cells were obtained by lavage during diagnostic fiberoptic bronchoscopy of 21 patients suspected of having lung malignancies. Of these patients 11 were diagnosed as having primary lung cancer (Group I) and included individuals with squamous cell carcinoma, adenocarcinoma, undifferentiated large and oat cell carcinoma at varying locations and TNM stages, 4 patients demonstrated nonprimary metastatic carcinoma (Group II), and 6 patients did not reveal detectable tumors by bronchoscopy or follow-up (Group III) and were included as study controls. We examined the ability of pulmonary alveolar macrophages (PAMs) lavaged from patients in each of the three study groups to phagocytose opsonized sheep red blood cells. Phagocytic activity varied among patients in the same and different study groups; however, no significant differences were observed in the phagocytic or tumoristatic activities of PAMs recovered from tumor-bearing and nontumor-bearing lung regions of the same patient. Moreover, lavage fluids collected from tumor-bearing regions did not suppress the phagocytic activity of PAMs collected from control lungs nor lung regions contralateral to the tumor-bearing lung. The data do not support the view that bronchial neoplasms or their secreted products suppress phagocytic functions of alveolar macrophages.

Adult↗
PubMed1982

Synthesis and bioevaluation of a series of alkyl ethers of p-N,N-bis(2-chloroethyl)aminophenol.

A series of even numbered normal alkyl ethers (C2-C14) of p-N,N-bis(2-chloroethyl)aminophenol were synthesized and evaluated as to acute toxicity in mice and effects on survival in L-1210 leukemic mice. All of the ether derivatives demonstrated significantly lower acute toxicity than the parent phenol mustard. Significant survival times (greater than or equal to 125%) were obtained with all compounds except the hexyl derivative. The decyl ether produced the greatest significant increase and the ethyl ether the lowest significant increase in mean survival time. Significant survival times were produced at four dosage levels for the butyl, decyl, and dodecyl derivatives, three dosage levels for the octyl and tetradecyl derivatives, and one dosage level for the ethyl derivative.

Aniline Mustard↗
PubMed1982

Synthesis and bioevaluation of a series of fatty acid esters of p-[N,N-bis(2-chloroethyl)amino]phenol.

A series of even numbered fatty acid esters (C2-C18) of p-[N,N-bis(2-chloroethyl)amino]phenol were synthesized and evaluated as to acute toxicity as well as effectiveness against L-1210 mouse leukemia. The acetate through the decanoate derivatives demonstrated toxicity between 2 and 3 times that of phenol mustard in HA/ICR mice. The less soluble laurate, myristate, palmitate, and stearate derivatives were less toxic. Significant survival times in the leukemia studies (T/C% greater than or equal to 125) were observed for all compounds except the acetate and hexanoate derivatives. The myristate derivative produced the greatest significant increase in survival time, 162%. The palmitate and stearate derivatives produced significant survival at five and four dosage levels, respectively. The butyrate and laurate derivatives produced significant survival at three dosage levels and the octanoate, decanoate, and myristate at two dosage levels.

Aniline Mustard↗
PubMed1982

Effects of microsomal enzyme induction on toxicity of p-N, N-bis (2-chloroethyl)aminophenyl alkyl ethers in mice and survival times in L-1210 leukemic mice.

Four alkyl ethers of p-N,N-bis(2-chloroethyl)aminophenol were selected to study the effects of microsomal enzyme induction by phenobarbital on the toxicity changes as reflected by LD50 and alteration of survival times in L-1210 leukemic mice. In the phenobarbital pretreated mice the LD50 for the ethyl ether of p-N,N-bis(2-chloroethyl)aminophenol was decreased from 1641 to 1213 microns/kg. This result suggests that O-dealkylation is the major metabolic pathway. The LD50 for the propyl ether of p-N,N-bis(2-chloroethyl)aminophenol was increased by the pretreatment from 605 to 678 microns/kg. The LD50 for the butyl ether was increased from 714 to 910 microns/kg. An additional metabolic pathway, (omega-1)-hydroxylation, is suggested for the propyl and butyl ethers. The hexyl ether appeared to be unaffected by the pretreatment; thus, O-dealkylation was ruled out as a major pathway. In the survival studies, the pretreatment reduced the antitumor effectiveness of the ethyl and the butyl ethers. The survival times were increased for some dose levels for the propyl ether. No significant trend in survival times was observed for the hexyl ether in the pretreated mice.

Animals↗
PubMed1981

Comparison of quantitation methods for L-1210 cell populations and evaluation of selected cytotoxic agents in leukemic mice.

A more rapid cell-counting technique using an electronic cell counter was developed as an improvement over the slower hemocytometer method. The electronic counting method produced cell counts that had a smaller standard deviation but were not significantly different from the hemocytometer method. The acetate, hexanoate, and decanoate esters of p-N,N-bis(2-chloroethyl)aminophenol were investigated for acute toxicity in mice, effects on survival times, and effects on L-1210 cell populations in L-1210 leukemic mice. The decanoate ester was the least toxic compound and was most effective in lengthening the lifespan of the mice. The acetate and hexanoate esters were more effective in reducing L-1210 cell populations.

Aniline Mustard↗
PubMed1975

Hydrolysis of fatty acid esters of acetaminophen in buffered pancreatic lipase systmes I.

A series of fatty acid esters of acetaminophen were prepared beginning with acetate, the propionate, and all even-numbered fatty acids and going through the octadecanoate. The enzymatic hydrolysis of all derivatives was studied in vitro with varying amounts of lipase assed to the hydrolysis mixtures. Under the conditions of the in vitro hydrolysis, it was observed that all derivatives were hydrolyzed more readily in an aqueous medium at pH 7.8. A positive relationship was seen between the hydrolysis rates and the concentration of lipase at this pH. There was a negative relationship between the chain length of the acyl moiety and the corresponding hydrolysis rates. The short chain esters were hydrolyzed at rates many times more rapid than the long chain esters. The intermediate chain-lenght ester, p-acetamidophenyl decanoate, p-acetamidophenyl laurate, and p-acetamidophenyl myristate, were hydrolyzed at intermedediate time periods extending over 12 hr, approaching completion at 97.5, 87.5, and 80.5%, respectively, when 18 Wilson units of lipase was used in each milliliter of hydrolysis mixture. The longer chain esters, p-acetamidophenyl palmitate and p-acetamidophenyl stearate, were hydrolyzed to the extent of 16 and 8%, respectively, over 12 hr under the same in vitro conditions.

Acetaminophen↗
PubMed1975

Blood concentration profiles of acetaminophen following oral administration of fatty acid esters of acetaminophen with pancreatic lipase to dogs.

Fatty acid esters of acetaminophen were administered orally to dogs, and blood concentrations of acetaminophen were determined at various time intervals. Blood concentrations of acetaminophen following oral administration of a short chain ester, p-acetamidophenyl acetate, were not significantly different from those found using acetaminophen. Blood concentrations of acetaminophen following oral administration of intermediate hydrocarbon chain-length compounds were less than those of the control at 1 and 3 hr postdosing. There appears to be a direct relationship between the in vitro hydrolysis rates and the blood concentration in vivo. Concomitant oral administration of acetaminophen derivatives, pancreatic lipase, and calcium salts resulted in an increase in the blood levels of acetaminophen as compared to administration of the esters alone. Calcium carbonate was included as a source of calcium ion to activate the lipase involved in the hydrolysis of the fatty acid esters. A combination of p-acetamidophenyl acetate, p-acetamidophenyl dodecanoate, pancreatic lipase, and calcium carbonate was shown to achieve a prolonged release of acetaminophen. p-Acetamidopheny acetate was thought to provide the initial release of acetaminophen; p-acetamidophenyl dodecanoate, being hydrolyzed more slowly, provided the prolonged release, which maintained therapeutic blood concentrations for 13 hr following a single dose of the combination in dogs.

Acetaminophen↗