Determination of glyceryl trinitrate and its two main metabolites in human plasma using a new sensitive gas chromatography method.

The aim of the present study was to determine the concentrations of nitroglycerin (glyceryl trinitrate, GTN, CAS 55-63-0) and its two main stable metabolites; 1,2-dinitroglycerin (1,2-glyceryl dinitrate, GDN, CAS 621-65-8) and 1,3-dinitroglycerin (1,3-GDN, CAS 623-87-0) in human plasma using a capillary gas chromatography method with an electron capture detection. Using the GC conditions, linear calibrations were obtained for 1,3-GDN from 0.14 to 3 ng/mL, for 1,2-GDN from 0.06 to 6 ng/mL, and for GTN from 0.01 to 0.3 ng/mL in plasma samples by the following calibration curve equations: [y = 0.1924x - 0.0088 (r = 0.999)], [y = 0.2273x + 0.0164 (r = 0.995)], [y = 17.434x - 0.0751] for 1,3-GDN, 1,2-GDN, and GTN respectively. The calculated limits of quantification values for GTN, 1,2-GDN, and 1,3-GDN were 0.03 ng/mL, 0.2 ng/mL, and 0.15 ng/mL respectively. This method was verified with a bioequivalence study of an Iranian brand of oral sustained release nitroglycerin with an innovator formulation.

Changes in plasma concentration of taurine in stroke.

Taurine is critical for proper brain functioning. Increase in plasma taurine concentration has already been shown in many diseases [1,2,5,10,12,14,17,22,25,47]. The plasma concentrations of taurine in 60 patients, suffering from stroke, were compared with that of 54 healthy volunteers. The plasma samples of the patients were obtained three times in the first five days of hospitalization. A Student's t-test showed a significant difference (P<0.0001) between the plasma concentrations of taurine of the patients group (136.5±8.2mmol/L) and the control group (41.9±2.5mmol/L). In addition, a one-way repeated measures ANOVA test showed that the mean plasma concentration of taurine in the patients during the first five days of hospitalization declined significantly from 136.9±8.2mmol/L in the first day of hospitalization to 120.1±5.9mmol/L on the third day and 110.2±7.0mmol/L by the fifth day (P>0.05). The plasma concentration of taurine was increased in the patients with stroke probably because of brain tissue damage. Although, according to the result of the study, mean plasma taurine concentration in stroke patients declined during five days of hospitalization. Further studies are needed to introduce taurine as a biomarker of recovery in stroke.

Pharmacokinetics of oral taurine in healthy volunteers.

Taurine, a sulfur-containing amino acid, is a normal constituent of the human diet. Little is known of the pharmacokinetics of taurine in man after oral administration. We studied the pharmacokinetics of 4 g taurine in eight healthy male volunteers (median age 27.5, range 22-45) following orally administration in the fasting state in the morning. Blood samples were taken at regular intervals and plasma taurine concentration was measured by a modified HPLC method. Data were subjected to noncompartmental analysis. Maximum plasma taurine concentration (C(max)) was measured at 1.5 ± 0.6 hr after administration as 86.1 ± 19.0 mg/L (0.69 ± 0.15 mmol). Plasma elimination half-life (T(1/2)) and the ratio of clearance/bioavailability (Cl/F) were 1.0 ± 0.3 hr and 21.1 ± 7.8 L/hr, respectively. Since taurine is occasionally used in therapeutics as a medicine, the pharmacokinetics and effects of oral taurine in healthy volunteers would be useful in the future studies of taurine in pharmacology and nutrition.

Pharmacokinetic and pharmacodynamic study of morphine and morphine 6-glucuronide after oral and intravenous administration of morphine in children with cancer.

The aim of this study was to characterize the pharmacokinetics and pharmacodynamics of morphine and morphine 6-glucuronide (M6G) in children with cancer. Serum concentrations of morphine and M6G in children who received single oral or short term continuous intravenous morphine were determined by HPLC and ELISA assays, respectively. The serum C(max) of morphine and M6G after i.v. morphine administration was 560.5 and 309.0 nM and the T(max) was 61 and 65 min, respectively. The elimination half-life was 140.0 and 328.7 min, respectively. After oral administration of morphine, the serum C(max) of morphine and M6G was 408.34 and 256.3 nM and the T(max) was 40.0 and 60 min, respectively. The half-life was 131.0 and 325.8 min, respectively. The side effects were: drowsiness (100%), nausea and/or vomiting (57%), pruritus (28%) and urinary retention (14%). There were no reports of respiratory complications. This study showed that pharmacokinetics factors of morphine and M6G in children were significantly different from adults. Therefore the required dose for children should be different from that of adults and should be based on studies performed on children rather than on studies on adults. Some adverse effects, particularly nausea and pruritus, may be commoner than is usually thought, while others, particularly respiratory problems did not occur.

Evaluation of taurine as a biomarker of liver damage in paracetamol poisoning.

Taurine is one of the most abundant amino acids in the body. Plasma taurine levels of 217 paracetamol positive and 100 paracetamol negative poisoned patients (related to non-hepatotoxic agents) referred to the Toxicology lab in Cardiff Poisons unit and 90 healthy humans (age between 18 and 45) were measured by a high performance liquid chromatography method. The data were analysed using linear regression and two-tailed unpaired student t-test using Prism software package. We showed that the mean plasma taurine concentration in the paracetamol-poisoned patients (mean 26.4+/-1.6 mg/l) was significantly different from the control groups (mean 5.6+/-0.2 mg/l) (P<0.0001) and the non-paracetamol group (mean 18.1+/-1.1 mg/l) (P<0.01). Taurine is produced by the liver in response to a toxic insult and subsequent leakage from damaged cells leads to increased concentrations in plasma and urine. Therefore a plasma or urinary taurine concentration could be a useful marker for paracetamol-induced hepatic damage.