Eileen Ruch

Diazepam concentrations in parotid saliva, mixed saliva, and plasma

The concentration of diazepam in the plasma and saliva of 9 normal human subjects receiving a single oral dose of diazepam (10 mg) over an 8‐hr period was determined by gas‐liquid chromatography/electron capture analysis. In addition, the binding of diazepam to plasma protein in these subjects was determined using equilibrium dialysis at specific time intervals corresponding to periods of plasma and saliva collection. A linear relationship was found between diazepam concentration in plasma and that in both mixed and parotid saliva, over plasma concentrations ranging from 196 ± 16.4 to 74.8 ± 10.3 ng/ml. The elimination constants (−Ke) were 0.13, 0.17, 0.18 for diazepam disappearance from plasma, parotid saliva, and mixed saliva, respectively. The mean parotid concentration ratio was 0.035 and the mixed saliva/plasma diazepam concentration ratio was 0.029. These were not affected by variations in plasma diazepam levels. The percentage of the plasma diazepam concentration in both parotid saliva (3.5%) and mixed saliva (2.9%) was of the same order as the fraction of diazepam found to be free from plasma protein in these subjects (2.0% to 3.5%). The results indicate that there is no significant difference between parotid saliva and mixed saliva concentrations over a period of 8 hr after a single oral dose of diazepam. The results strongly suggest that the appearance of diazepam in saliva may provide an alternate, non invasive method of determining plasma diazepam levels.

The presence of cocaine and benzoylecgonine in rat cerebrospinal fluid after the intravenous administration of cocaine.

Cocaine hydrochloride, in doses of 0.5, 1.0, 2.0 and 4.0 mg/kg, iv, was administered to male Sprague-Dawley rats. Cerebrospinal fluid (CSF) was collected from the cisterna magna over a 20 min period and blood samples were obtained at 20 min after cocaine administration. In addition, blood samples for the 1 mg/kg dose of cocaine were collected at 2, 10, 20 and 30 min following drug injection. Gas chromatography/mass spectrometry was used for the analysis of cocaine and its metabolites in plasma and CSF. The disappearance of cocaine (1 mg/kg) from the plasma exhibited first order kinetics with a half-life of 18.11 +/- 3.22 min. Cocaine and benzoylecgonine were found in CSF and the concentrations of cocaine and benzoylecgonine increased in CSF as the doses of cocaine were increased. CSF flow rates were not altered by the iv administration of cocaine or benzoylecgonine. The CSF-to-plasma ratios for cocaine were quite similar to each other over the dosage range of cocaine that was administered; however, the CSF-to-plasma ratios for benzoylecgonine decreased as the concentrations of benzoylecgonine increased in plasma and CSF. When benzoylecgonine (2 mg/kg, iv) was given, the compound was detected in CSF indicating that benzoylecgonine can enter into the central nervous system from the peripheral blood. This investigation shows that cocaine and benzoylecgonine can be assayed in CSF and that the plasma levels of these compounds correlate with their concentrations in CSF.

The accumulation and disappearance of cocaine and benzoylecgonine in rat hair following prolonged administration of cocaine

Hair samples were obtained at various time periods from male Sprague-Dawley rats following the injection of cocaine hydrochloride in doses of 5, 10, and 20 mg/kg, ip, for 28 days. Hair samples were also taken continually after the dosing was stopped until the presence of cocaine and benzoylecgonine were no longer detected in hair. Cocaine and benzoylecgonine in hair and plasma were analyzed by gas chromatography/mass spectrometry. Both cocaine and benzoylecgonine were found in hair samples 4 days after the initiation of cocaine administration. When cocaine dosing was stopped after 28 days, approximately 25 to 30 days were required for cocaine and benzoylecgonine to disappear from rat hair in the group of animals that received the highest dose of cocaine. The disappearance of cocaine and benzoylecgonine followed first-order kinetics. The mean rate constant and mean half-life for cocaine disappearance from hair were 0.212 +/- 0.005 day-1 and 3.31 +/- 0.09 days, respectively, and the mean rate constant and mean half-life for benzoylecgonine disappearance from hair were 0.098 +/- 0.006 day-1 and 6.90 +/- 0.28 days, respectively. The mean plasma concentrations of cocaine on Day 25 for the 5, 10, and 20 mg/kg doses of cocaine were 508 +/- 42, 852 +/- 95, and 2027 +/- 75 ng/mL, respectively, and the mean plasma benzoylecgonine levels for the 5, 10, and 20 mg/kg doses of cocaine were 49.9 +/- 7.0, 103.3 +/- 9.3, and 191.0 +/- 16.0 ng/mL, respectively. There was a positive correlation between the doses of cocaine hydrochloride administered and the plasma levels of both cocaine and benzoylecgonine. This study showed that cocaine and benzoylecgonine can be measured in rat hair following the administration of cocaine and that it was possible to correlate the concentrations of cocaine and benzoylecgonine found in hair with the doses of cocaine that were administered.

Correlations of parotid saliva and blood ethanol concentrations

Abstract This paper is devoted to the detection and quantitation of blood and parotid saliva ethanol in both human subjects and rats. The human ethanol saliva-plasma ratio has been determined to be 1.04 utilizing a collection technique which is non-invasive and easily performed. The rat ethanol saliva-plasma ratio has been found to be 1.21 with a direct cannulation technique of the parotid duct. Differences between the human and rat ratios have been attributed to the method of salivary gland stimulation. The human parotid gland was stimulated by a reflex action of an organe-flavored lozenge, whereas the rat parotid gland was stimulated by a direct infusion of pilocarpine. The results indicate that the rat parotid secretion of ethanol is very similar to the human secretions, and the rat could possibly be utilized as an animal model for future alcohol salivary studies.

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.

Detection and quantitation of phencyclidine in rat parotid saliva and plasma

Phencyclidine (PCP, Angel Dust) is one of the most commonly abused hallucinogens in today’s society. Owing to the increased incidence of toxicological problems associated with this drug, the identification and quantification of phencyclidine is of prime importance both from a medical as well as a legal point of view. As a result of this interest, various analytical procedures have been developed, including thin-layer chromatography [l] , gas chromatography [ 21 and radioimmunoassay [ 31. In addition, the quantitation of PCP in several biological specimens has been accomplished, including blood, plasma, urine and, recently, mixed rat saliva [ 41. Recent interest has developed concerning the effects and detection of PCP in saliva owing to the earlier report that PCP can cause a hypersalivation syndrome in some individuals [ 51. The investigation presented here had two major objectives: (1) to determine the effects of PCP on parotid salivary secretions in rats and (2) to identify and quantify PCP in rat parotid saliva using two different dosages and to calculate the corresponding parotid saliva/plasma ratios.