Plasma kinetics and urinary elimination of saccharin in man

The plasma kinetics and urinary elimination of saccharin were studied in 3 groups each of 5 healthy male volunteers given the sweetener as three different single oral doses (50, 150 and 333 $\text{mg}\text{60 kg}$ body weight). Saccharin concentrations were determined by gas liquid chromatography-stable isotope dilution mass fragmentography.The compound was rapidly absorbed through the gastrointestinal tract, reaching plasma peak concentrations between 30 and 60 min after intake. Plasma saccharin elimination was also fast, with a monoexponential pattern of decay. At the 3 doses studied saccharin was excreted in urine within a few hours, about 60% of the dose being excreted unchanged at 6 h and 76% at 24 h.     

Plasma and urinary excretion kinetics of oral baclofen in healthy subjects

Summary Baclofen, a centrally acting muscle relaxant, is used in the treatment of spasticity. Its pharmacokinetics has been derived from plasma and urine data in four healthy subjects, whose renal function was simultaneously measured.After oral administration of a single 40 mg dose, baclofen was mainly excreted unchanged by the kidney, 69 (14) %. The half-life, calculated from extended least squares modelling (ELSMOS) both of plasma and urine data was 6.80 (0.68) h, which is longer than reported in most studies based solely on plasma data.The renal excretion rate constant had the high mean value of 0.35 (0.24) h^–1, and the apparent renal clearance of baclofen equalled the creatinine clearance. Passive tubular reabsorption is relatively unimportant, since no dependence was observed on variables urine flow or pH.Although active tubular secretion may contribute to its renal clearance, as shown by the effect of coadministration of probenecid, glomerular filtration appears to be the dominant transport mechanism.     

Urinary primaquine excretion and red cell methaemoglobin levels in man following a primaquine:chloroquine regimen.

1 Red cell methaemoglobin levels were found to be significantly raised in healthy subjects given a 14-day course of primaquine with chloroquine on the first 3 days. 2 The methaemoglobin levels were not related to the quantity of primaquine excreted. 3 No primaquine could be detected in the plasma at 24 h following the last three daily doses.     

Studies on kinetics of anturan excretion in man.

The kinetics of anturan excretion was studied. Experiments were carried out on ten healthy volunteers. The drug was given orally once applying three different doses: 100, 200, 400 mg. The contents of the drug in urine were determined by means of the modified method worked out by Wallace. It was found about 42 per cent of the dose was excreted with urine in an unchanged form. The process of anturan excretion may be described according to the one-compartment open kinetic model. The half-life of excretion is 3.5 hours, the excretion constant is 0.20. The formula showing the course of anturan excretion in time has been given. Five examples of the quantitative exposure test have been proposed; they allow the calculation of the absorbed drug dose and thus the degree of poisoning. The test can be also helpful in controlled therapy.     

Plasma concentrations and urinary excretion of the antiarrhythmic quaternary ammonium compound QX-572 in man

Summary A quantitative thin layer chromatographic (TLC) method has been developed for determination of the antiarrhythmic quaternary ammonium compound N, N-bis (phenylcarbamoylmethyl) dimethylammonium chloride (QX-572) in biological materials. Prior to chromatography QX-572 was transferred into chloroform as perchlorate by ion pair extraction. Tritium-labelled QX-572 was used as the internal standard and a TLC scanning spectrophotometer equipped with a linear detector system afforded the required accuracy, specificity and simplicity. The method was used to determine QX-572 in plasma from 11 patients with various cardiac diseases who received QX-572 8 mg/kg body wt. as an intravenous infusion over 30 min. There was a rapid initial decay of the plasma levels from 11.0±1.1 µg/ml (mean ± SE) at the end of infusion to 3.5±0.5 µg/ml after 30 min. 240 min after commencement of the infusion the plasma level was 0.7±0.1 µg/ml. In these patients 22±2% (mean±SE) of the total administered dose of QX-572 was excreted unchanged in urine during the 24 hours following infusion of the drug. A second group of 28 patients with acute myocardial infarction also received QX-572 8 mg/kg body wt. Their plasma levels did not differ significantly from those found in the first group of patients. There was a poor correlation between the amount of QX-572 administered and plasma level at the end of the infusion. The study has provided some preliminary data about the pharmacokinetics of QX-572, but before a detailed analysis can be done data from longer periods of observation is required. The present results suggest that in future QX-572 can be administered in a standardized dosage, what would be advantageous in practice.     

Plasma kinetics of DDAVP in man

After a bolus injection, DDAVP was infused in normal volunteers over a period of 3 1/2 hours. Blood was sampled during and after the infusion and was analyzed for DDAVP using a specific RIA. The total clearance for DDAVP was 2.6 ml/min./kg b.wt., and half-life in plasma 55 min.     

Effects of age and chronic renal failure on the urinary excretion kinetics of famotidine in man

Summary The plasma and urine concentrations of famotidine, a new, potent H₂-receptor antagonist, have been measured in 16 healthy young adults, 8 healthy elderly people and 18 patients with varying degrees of renal dysfunction after intravenous administration.Both the plasma elimination and renal excretion of famotidine were decreased in the elderly volunteers and renal patients. The renal clearance of famotidine averaged 4.43 ml/min/kg (310 ml/min) in normal young volunteers, which exceeded the mean creatinine clearance 1.55 ml/min/kg (109 ml/min), suggesting net secretion is a significant mechanism for elimination of famotidine.The ratio of famotidine renal clearance to creatinine clearance decreased as creatinine clearance decreased; these results suggest that the deterioration in the secretion process was much faster than that in glomerular filtration and are incompatible with the intact nephron hypothesis. Nevertheless, both total body clearance and renal clearance were significantly correlated with creatinine clearance.The apparent half-life was also significantly correlated with creatinine clearance. Since famotidine is essentially free of dose-related adverse effects, dose adjustment in patients with mild renal insufficiency and in elderly people is not required; however, either a prolonged dosing interval or a decrease in daily dose during long-term therapy may be adapted for the patients with severe renal insufficiency to avoid accumulation and the potential undesirable effects.     

The urinary excretion of gamma-hydroxybutyric acid in man

gamma-Hydroxybutyric acid (GHB) has been widely associated with drug-facilitated sexual assault (DFSA). However, its excretion profile in man has not been well characterized. To assess the detectability of GHB for forensic cases and to correlate urinary levels with dose, we have examined the excretion profiles of 1- and 2-g doses of GHB (sodium salt) in a healthy male volunteer. The urinary levels were measured by a novel, simple and highly reproducible method. The drug was found to be excreted in small amounts in the free form (0.86 and 1.16% for 1- and 2-g doses, respectively) rapidly in urine (< or = 10 h). The urinary levels were found to be in the low mg L(-1) range (up to 29.1 mg L(-1)). The work presented demonstrates that it is of the utmost importance to collect the samples as soon as possible following the alleged assault.     

Plasma kinetics, metabolism, and urinary excretion of alpha-lipoic acid following oral administration in healthy volunteers

R(+)-alpha-lipoic acid is a natural occurring compound that acts as an essential cofactor for certain dehydrogenase complexes. The redox couple alpha-lipoic acid/dihydrolipoic acid possesses potent antioxidant activity. Exogenous racemic alpha-lipoic acid orally administered for the symptomatic treatment of diabetic polyneuropathy is readily and nearly completely absorbed, with a limited absolute bioavailability of about 30% caused by high hepatic extraction. Although the pharmacokinetics of the parent drug have been well characterized in humans, relatively little is known regarding the excretion of alpha-lipoic acid and the pharmacokinetics of any metabolites in humans. In the present study, plasma concentration-time courses, urinary excreted amounts, and pharmacokinetic parameters of alpha-lipoic acid metabolites were evaluated in 9 healthy volunteers after multiple once-daily oral administration of 600 mg racemic alpha-lipoic acid. The primary metabolic pathways of alpha-lipoic acid in man, S-methylation and beta-oxidation, were quantitatively confirmed by an HPLC-electrochemical assay newly established prior to the beginning of this study. Major circulating metabolites were the S-methylated beta-oxidation products 4,6-bismethylthio-hexanoic acid and 2,4-bismethylthio-butanoic acid, whereas its conjugated forms accounted for the major portion excreted in urine. There was no statistically significant difference in the pharmacokinetic parameters Cmax, AUC, and tmax between day 1 and day 4. Despite the prolonged half-lives of the major metabolites compared to the parent drug, no evidence of accumulation was found. Mean values of 12.4% of the administered dose were recovered in the urine after 24 hours as the sum of alpha-lipoic acid and its metabolites. The results of the present study revealed that urinary excretion of alpha-lipoic acid and five of its main metabolites does not play a significant role in the elimination of alpha-lipoic acid. Therefore, biliary excretion, further electrochemically inactive degradation products, and complete utilization of alpha-lipoic acid as a primary substrate in the endogenous metabolism should be considered.     

Plasma concentrations and excretion of zipeprol in man under acidic urine conditions.

Plasma concentrations of zipeprol, and the urinary excretion of it and two of its basic metabolites, compound II and compound III were examined after oral administration of zipeprol hydrochloride to man. The drug was rapidly and extensively metabolized, and the amount of unchanged drug excreted in the acidic urine varied from 1-5% of the dose; the two basic metabolites accounted for 19-38% of the dose.     

Plasma elimination and urinary excretion of methapyrilene in the rat

The metabolism and elimination of methapyrilene (2-[(2-dimethylaminoethyl)-2-thenylamino]pyridine) were characterized after the iv administration of 0.7 mg/kg or 3.5 mg/kg methapyrilene HCl plus [14C]methapyrilene HCl to adult male Fischer-344 rats. Approximately 40% and 35% of the administered dose was excreted in the urine in the first 24 hr in the low and high dose groups, respectively, as determined by liquid scintillation spectrophotometry. Fecal excretion accounted for 38% and 44% of the administered dose in the first 24 hr in the low and high dose groups, respectively, as confirmed via combustion analysis. The 24-hr urinary metabolic products consisted of one major and five minor radiolabeled compounds. The major metabolite was isolated with reversed-phase HPLC and identified as methapyrilene N-oxide. This was accomplished by comparison of the chromatographic and mass spectral characteristics of this metabolite with that of authentic methapyrilene N-oxide. Methapyrilene and mono-N-desmethyl methapyrilene also were identified after isolation with reversed-phase HPLC and comparison of their mass spectral and/or chromatographic properties with those of authentic compounds. The plasma metabolic profile was essentially the same as the urinary profile. The elimination of methapyrilene from plasma occurred through a first-order process. The terminal plasma elimination t1/2 of methapyrilene did not increase with increasing doses (2.75 hr, 0.7 mg/kg; 2.81 hr, 3.5 mg/kg); thus, methapyrilene does not exhibit dose-dependent elimination over this 5-fold dose range.     

Elimination kinetics and urinary excretion of disopyramide in human healthy volunteers

Elimination kinetics and the renal handling of disopyramide was examined in 8 healthy volunteers. Approximately 50% of the administered disopyramide undergoes hepatic metabolism (metabolic clearance = 116.1 +/- 42.2 ml/min.), while the rest is excreted by the kidneys (renal clearance = 101.9 +/- 21.6 ml/min.). Total renal excretion rate of disopyramide was 0.676 +/- 0.188 mumol/min. and 0.258 +/- 0.029 mumol/min. was excreted by glomerular filtration leaving a net tubular secretion of 60% of the total renal elimination. A significant positive correlation was observed between total serum concentrations and renal clearance values of disopyramide while no significant correlation could be obtained between serum concentrations of the unbound drug and renal clearance values of disopyramide, implying a constant value of unbound renal clearance. Hepatic blood flow was significantly (P less than 0.005) decreased following disopyramide infusion.     

Effect of urinary pH on the plasma and urinary kinetics of remoxipride in man

Summary The influence of urinary pH on the plasma and urinary kinetics of remoxipride in man has been studied in an open crossover trial in ten healthy male volunteers. Ammonium chloride (urinary pH 5.2) and sodium hydrogen carbonate (urinary pH 7.8) were used as pretreatments on two occasions in randomized order. On each occasion remoxipride 50 mg solution was administered orally and plasma and urinary concentrations of the drug were determined by HPLC and plasma prolactin concentrations by RIA.Remoxipride was rapidly distributed in the body according to a one-compartment model. The mean plasma elimination half-life (t_1/2) was 3.6 h in the ammonium chloride experiment and 6.2 h in the sodium hydrogen carbonate experiment. The mean plasma clearance of remoxipride was 141 and 89.9 ml·min^–1 in the acidic and alkaline conditions, respectively, and the corresponding mean renal clearances were 58.5 ml·min^–1 and 11.7 ml·min^–1. The urinary excretion of remoxipride up to 72 h after drug administration was 43.1% and 12.3% following acidification and alkalinization, respectively. Remoxipride induced a similar rapid, transient elevation of plasma prolactin under both conditions.Thus, the urinary pH has a marked effect on the elimination kinetics of remoxipride. After an overdose, treatment with ammonium chloride might be valuable in hastening elimination of remoxipride from the body.