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Biomedical subjects

G J DiGregorio

Publications and source records attributed to G J DiGregorio.

At least 37 records · Page 2Linked to original sources
PubMed1983

Effect of cimetidine on the pharmacokinetics of quinidine and lidocaine in the rat.

Because of previously reported drug interactions involving cimetidine and liver-metabolized drugs, the intravenous pharmacokinetics of quinidine (25 mg/kg) and lidocaine (15 mg/kg) were investigated in anesthetized rats pretreated with a single intraperitoneal dose of cimetidine (60 mg/kg) and compared with saline pretreated controls. Significant reductions of 35 and 23% in the respective total clearances of quinidine and lidocaine were observed in the presence of cimetidine. The quinidine volume of distribution was significantly decreased in the cimetidine-treated rats, while the lidocaine volume of distribution was not altered significantly. There was no significant change in the elimination half-life for either drug in the presence of cimetidine. These results suggest cautious use of quinidine or lidocaine when cimetidine is prescribed concurrently.

Animals↗
PubMed1983

Doxorubicin and 5-fluorouracil plasma concentrations and detectability in parotid saliva.

Doxorubicin and 5-fluorouracil pharmacokinetics were studied in 19 volunteers with various advanced neoplastic diseases who received 50-90 mg doxorubicin or 600-1000 mg 5-fluorouracil intravenously, followed by plasma and parotid saliva collection over a 75 min period. The extent to which these chemotherapeutic agents are bound to plasma proteins, at concentrations chosen to approximate plasma concentrations, was measured by equilibrium dialysis. Both agents were quantitated by high-performance liquid chromatography. As reported previously, a wide range of plasma levels were found among patients receiving similar doses of either doxorubicin or 5-fluorouracil. It appears that in addition to being quickly cleared from the plasma both chemotherapeutic agents are excreted in detectable amounts in parotid saliva, a route of elimination heretofore given little or no attention. Excretion in the saliva exposes the mucosa of the upper gastrointestinal tract to 5-fluorouracil after intravenous administration and may play a part in causing stomatitis in patients receiving it by this route. Since there are huge interindividual and pronounced intraindividual differences in S/P ratios mostly not systematically related to the drugs' concentration in plasma, the concentration in parotid saliva was not useful in predicting the level of free doxorubicin or 5-fluorouracil in plasma.

Aged↗
PubMed1983

The effect of thermal injury on drug metabolism in the rat.

Because of previously reported hepatic abnormalities in burns, the activity of the hepatic drug metabolizing system was assessed in burned Sprague-Dawley rats. In 16% burned male rats, pentobarbital sleeping times were significantly prolonged from day 1 to day 24 postburn, and trichloroethanol sleeping times were significantly prolonged from day 1 to day 10 postburn. The activity of p-nitroanisole O-demethylase was significantly depressed in male rats at 5, 10, and 17 days post-16% burn. In female rats, this enzyme was more depressed at 10 days post-16% burn than in male rats. A direct relationship was found between per cent burn and impairment of enzyme activity. The depression of drug metabolizing enzymes was inducible by phenobarbital pretreatment. Pretreatment with the immunosuppressive drug azathioprine prevented the enzyme depression at 5 days postburn, a result which possibly implicates a postburn hyperimmune response as the mechanism for the depressed enzyme levels.

Animals↗
PubMed1982

Investigation of digoxin, quinidine, and disopyramide interactions in rats utilizing parotid saliva, blood, and other tissues.

Blood, parotid saliva, heart, liver, and kidney concentrations of digoxin and quinidine were determined in rats chronically treated with digoxin and in nontreated (control) rats after the administration of quinidine (20 mg/kg ip) and disopyramide (10 mg/kg ip). The results indicated that digoxin concentrations increased significantly and proportionally in parotid saliva and plasma after quinidine, but did not increase after disopyramide. With the exception of the liver, which showed an increase in digoxin concentrations, tissue concentrations of digoxin did not differ from control animals. In rats pretreated chronically with digoxin, quinidine concentrations in plasma, parotid saliva, or heart tissue did not differ significantly from control animals, but were significantly lower than controls in liver and kidney tissues. The results presented here lend additional support to the hypothesis that the increase in digoxin plasma concentration following quinidine administration is primarily due to interference with renal excretion and displacement of digoxin by quinidine binding sites. Furthermore, its was demonstrated that disopyramide has little or no effect on plasma digoxin levels in rats.

Animals↗
PubMed1982

Pharmacokinetics of procainamide in rats with extrahepatic biliary obstruction.

The pharmacokinetics of the widely used antiarrhythmic agent, procainamide, was studied in rats with extrahepatic biliary obstruction produced by ligation of the common bile duct. Various biological fluids, including plasma, saliva, and urine, were analyzed for procainamide and/or its major metabolite, N-acetylprocainamide. Ligation of the common bile duct immediately prior to intravenous administration of 50 mg/kg procainamide did not alter plasma, saliva, or urine concentrations of procainamide, indicating that biliary excretion was of minor importance in the elimination of procainamide. However, bile duct ligation allowed to persist for 4 days significantly elevated plasma, saliva, and urine levels of procainamide. While the increase in urinary procainamide paralleled the increase observed in plasma, salivary concentrations did not. Bile duct ligation did not appear to impair nonmicrosomal acetylation of procainamide, although a significantly greater amount of unchanged drug was found in the urine after 24 hr. Pharmacokinetic analysis via the two-compartment open model showed that bile duct ligation caused a decrease in overall clearance from approximately 61.94 to 28.71 ml/kg/min. This reduction probably resulted from the decreased microsomal metabolism of procainamide. The significant reduction in the apparent volume of distribution from 3.76 to 2.72 liter/kg could be the result of reduced binding sites. There was also a significant increase in the elimination half-life of procainamide from 47.39 to 78.64 min in bile duct ligated rats.

Animals↗
PubMed1982

Excretion of procainamide into bile and saliva in rats with chronic renal failure.

The excretion of the widely used antiarrhythmic agent procainamide into the bile and saliva of rats with chronic renal failure (CRF) induced by a two stage-total nephrectomy was studied. Chronic renal failure significantly elevates plasma, salivary, and biliary procainamide levels compared to normal and sham operated rats at all time periods studied. However, while the increase in salivary excretion parallels that of plasma, biliary excretion does not. Results indicate that there is probably saturation of an active transport mechanism for procainamide into bile and that bile cannot compensate for increased drug levels which accumulate during CRF. Salivary excretion, though increased during CRF, also cannot compensate for elevated procainamide levels. Moreover, CRF does not appear to impair non-microsomal acetylation of procainamide, the major biotransformation reaction in the metabolism of this drug.

Acecainide↗
PubMed1982

Antiemetics.

Explore the source record for details and available documents.

Adrenal Cortex Hormones↗
PubMed1980

Human whole blood and parotid saliva concentrations of oral and intramuscular promethazine.

Ten healthy male subjects received 25 mg of promethazine intramuscularly, followed within 3 weeks by oral administration of 25 mg. Whole blood and parotid saliva were collected over a 12-hr period after drug administration. Promethazine was quantitated by high-performance liquid chromatography. After intramuscular administration, the promethazine concentrations were 3.0-22.4 ng/ml in blood and 0.9-2.8 ng/ml in parotid saliva. After oral administration, the promethazine concentrations were 1.4-5.5 ng/ml in blood and 0.2-0.8 ng/ml in parotid saliva. The peak blood promethazine concentration after the intramuscular dose was four times higher than that following the oral dose, which indicates that promethazine possesses an extensive first-pass effect. The mean parotid saliva to whole blood ratio (S/B) was calculated to be 0.24 after the intramuscular route an 0.20 after the oral route over the 12-hr period. The calculated percentage of free drug in the blood was 20-24% of the whole blood concentration determined from the S/B ratio.

Administration, Oral↗
PubMed1980

Quantitation and comparison of phenobarbital levels in the plasma, saliva, and cerebrospinal fluid of the rat, and the demonstration of an alteration of drug passage by ethanol.

In this study, the ability and extent of three biological fluids--plasma, saliva, and cerebrospinal fluid--to compartmentalize intravenously administered phenobarbital was examined and correlated. The three fluid compartments show markedly different levels of phenobarbital, though this probably does not reflect qualitative differences in the barriers that separate them, but rather in the nature of the compartments themselves. In addition to the quantitation and correlation of drug levels in the various compartments, intravenous administration of 400 mg/kg ethanol following the intravenous administration of 20 mg/kg phenobarbital was shown to alter the passage of phenobarbital into the different fluid compartments, causing a significant increase in the phenobarbital level of cerebrospinal fluid as compared to controls receiving no ethanol. Though the effect seen in the cerebrospinal fluid is significant, while the effect in saliva is not (though the trend was present), it is felt that the action of ethanol to alter drug passage is a non-specific effect on the vasculature. This finding of altered drug passage may help explain the observed synergistic interaction of ethanol and various sedative drugs.

Animals↗
PubMed1979

Correlations of parotid saliva and plasma lidocaine concentrations in rats.

The concentration ratios of parotid saliva to plasma lidocaine were determined in rats after a single dose (10 mg of lidocaine/kg) and constant infusion (60 micrograms of lidocaine/kg/min). Parotid saliva and plasma samples were obtained at 10, 20, and 30 min after single-dose lidocaine administration and at 70, 80, and 90 min after the initiation of a lidocaine infusion. The saliva/plasma concentration ratios for lidocaine after single-dose administration decreased from 1.13 +/- 0.03 at 10 min to 0.51 +/- 0.06 at 30 min, whereas the ratios determined during the lidocaine infusion remained constant (0.43 +/- 0.03, 0.45 +/- 0.03, and 0.43 +/- 0.04) over the time period tested. The variable saliva/plasma concentration ratios obtained after single-dose administration may be associated with rapid drug distribution between the plasma and peripheral compartments and variation in lidocaine binding to plasma proteins. However, during constant lidocaine infusion, a steady-state concentration was achieved within 70 min, as demonstrated by the constant saliva/plasma concentration ratios.

Animals↗
PubMed1979

In vitro study of antispasmodic effects of dicyclomine hydrochloride on vesicourethral smooth muscle of guinea pig and rabbit.

Dicyclomine inhibition of acetylcholine-induced and barium chloride-induced isotonic contractions of the smooth muscle from three segments of the lower urinary tract (bladder body, bladder base, and proximal urethra) of the guinea pig and the rabbit was studied in vitro. In the guinea pig dicyclomine caused competitive inhibition of acetylcholine-induced contraction of the bladder body (1 x 10(-7) M to 1 x 10(-5) M) and the bladder base (1 x 10(-6) M, 1 X 10(-5) M) and was less potent than atropine and propantheline. In the rabbit significant blockade of acetylcholine-induced contractions occurred at dicyclomine concentrations of 5 x 10(-6) M to 3 x 10(-5) M in the bladder body and at 1 x 10(-5) M and 3 x 10(-5) M in the bladder base. In both species dicyclomine inhibitory effects were most marked in the bladder body, moderate in the bladder base, and minimal in the proximal urethra. Dicyclomine failed to cause inhibition of the barium chloride-induced contractions in the guinea pig vesicourethral smooth muscle. In rabbits, however, significant antagonism P less than 0.01) of barium chloride-induced muscle contraction was observed with dicyclomine at concentration 1 x 10(-5) M in both bladder body and the bladder base. The clinical implication of such properties of dicyclomine are discussed.

Acetylcholine↗
PubMedDate not supplied

The interaction of dopamine, cocaine, and cocaethylene with ethanol on central nervous system depression in mice.

The interactions between dopamine, cocaine, cocaethylene, and ethanol were studied in Swiss-Webster mice. The loss of the righting reflex (LORR) was used as a measure of CNS depression. Animals were injected intraperitoneally (IP) with ethanol (4.0 g/kg). which caused a LORR. Immediately upon regaining of the righting reflex, mice were injected intracerebroventricularly (ICV) with saline, dopamine (0.1, 0.5, or 1.0 mumol/kg), cocaine (1, 15, or 25 mumol/kg), or cocaethylene (1, 15, or 25 mumol/kg). In the presence of systemic ethanol, all three compounds produced CNS depression in a dose-dependent manner. The dopamine D2-receptor antagonist sulpiride and the D1-receptor antagonist fluphenazine were given acutely ICV with dopamine in the presence of systemic ethanol to examine whether these antagonists could block the return to the LORR produced by dopamine. Sulpiride, however, actually enhanced the interaction between ethanol and dopamine in a dose-dependent manner as measured by the LORR; fluphenazine neither blocked nor enhanced the effect of dopamine in the presence of systemic ethanol. In addition, these antagonists had no effect on cocaine- and cocaethylene-induced CNS depression in the presence of systemic ethanol. The results of this study showed that the neurotransmitter dopamine and both cocaine and cocaethylene can promote further CNS depression in the presence of systemic ethanol, and that dopamine was significantly more potent than cocaine and cocaethylene as measured by the return to the LORR.

Animals↗