Pharmacokinetics of pantoprazole following single intravenous and oral administration to healthy male subjects

Summary The plasma pharmacokinetics of pantoprazole have been investigated following single intravenous infusion and single oral administration at a dose of 40 mg to 12 healthy male subjects in a randomised cross-over study. Both treatments were generally well tolerated and no relevant compound-related adverse events were noted. The plasma pharmacokinetics of pantoprazole following intravenous infusion in this group of subjects were characterised by a total plasma clearance of 0.13 l·h⁻¹·kg⁻¹ and apparent terminal elimination half-life 1.9 h. The apparent volume of distribution estimated at steady state (0.171·kg⁻¹) was compatible with the localization of a major fraction of the compound in extracellular water. Following oral administration as an enteric-coated tablet formulation, a variable onset of absorption was followed by rapid attainment of maximum plasma concentrations of pantoprazole. Pantoprazole was well absorbed following oral administration; the absolute systemic bioavailability of the compound was estimated as 77% (95% CI, 67 to 89%).     

Pharmacokinetics and metabolism of isosorbide-dinitrate after intravenous and oral administration

Summary The bioavailabilities of a conventional and two slow release 20 mg isosorbide dinitrate (ISDN) formulations were compared after oral administration in a three way cross-over study in 8 male volunteers. In a further group of 6 male volunteers the pharmacokinetics and metabolism of ISDN were investigated after intravenous infusion of a median dose of 14.1 mg for 2.5 h. A new analytical procedure was developed for the determination of isosorbide-5-mononitrate-2-glucuronide (IS-5-MN-2-Glu) and of isosorbide (IS). Kinetic data analysis on a molar basis was performed by the program package KINPAK providing model independent parameters. The median elimination half-lives of ISDN, IS-5-MN, IS-2-MN and IS-5-MN-2-Glu were 0.7, 5.1, 3.2 and 2.5 h, respectively. The systemic clearance of ISDN was 3.7 l/min and the distribution volume 2521 (3.1 l/kg). Apart from IS-5-MN-2-Glu, with a renal clearance of 5.9 l/min which suggested substantial glucuronidation in the kidney, the renal clearances of ISDN, IS-5-MN, IS-2-MN and the corresponding amounts excreted were negligible. 27.8% of the administered ISDN was excreted as IS-5-MN-2-Glu (8.7%) and IS (19.1%). Calculations based on the two mononitrate metabolites formed from ISDN showed an incomplete recovery of 84.1%, leading to the assumption that a simultaneous denitration to IS must have occurred. The rate of denitration at each nitro group in ISDN was almost twice as high as for the same position in the corresponding mononitrate. The bioavailability of the conventional ISDN formulation was 19%, although complete absorption was indicated by comparison of the percentages of mononitrate metabolites formed after the different routes of administration. On the same basis the absorption of the two sustained release formulations was found to be poor.Preliminary results were presented at the 2nd World Conference on Clinical Pharmacology and Therapeutics, Washington, 1983     

Pharmacokinetics of proxyphylline in adults after intravenous and oral administration

Summary Serum concentrations and urinary excretion of proxyphylline have been measured in five healthy adults after intravenous (29 µmol/kg), single oral (21 µmol/kg) and multiple oral (21 µmol/kg three times a day) doses to produce steady state. The mean peak time after oral administration was 29 min. The mean fraction absorbed was 1.09 calculated from serum concentrations, and 1.05 calculated from urinary excretion of the drug. The apparent volume of distribution was 0.61 l/kg (0.53–0.72 l/kg), 26% higher in males than in females. A two-compartment open model was found to describe the decline in the serum concentrations, giving a mean distribution half-life of 6 min. The intersubject ranges of biological half-life were 8.1–12.1 h and 8.3–12.6 h calculated from serum and urine data, respectively. 24% (18–29%) of the dose was excreted unchanged in urine, which agreed with the relationship between the calculated total body clearance and the renal clearance of the drug.Fellow of the Norwegian Research Council for Science and the Humanities     

Pharmacokinetics of ketorolac tromethamine in humans after intravenous,intramuscular and oral administration

Summary The pharmacokinetics of ketorolac tromethamine, a potent non-narcotic analgesic agent used for relief of moderate to severe pain, has been studied in 15 healthy volunteers who received single 10 mg doses intravenously (i.v.), intramuscularly (i.m.) and orally (p.o.) in a three-way cross-over design.The kinetics of i.v. ketorolac were characterized by a terminal half-life of 5.09 h, a small plasma clearance (CL = 0.35 ml·min^–1·kg^–1) and a small tissue distribution (V_ss=0.111·kg^–1, V=0.17 l·kg^–1; mean (SD). Following i.m. and p.o. administration, peak levels of approximately 0.8 µg/ml were rapidly attained (t_max = 0.8 and 0.9 h, respectively) and the systemic bioavailability was essentially complete.     

Pharmacokinetics of chlorpheniramine after intravenous and oral administration in normal adults

Summary Plasma and urinary levels of chlorpheniramine (CPM) and its 2 demethylated metabolites were measured by HPLC after i.v. and oral dosing. In 5 mg (maleate) i.v. bolus studies in 2 subjects, plasma CPM levels were fitted to triexponential equations with terminal half-lives (t _1/2) of 23 and 22 h and area of 3.6 and 3.21/kg, respectively. Intravenous data predicted hepatic blood extraction ratios for the 2 subjects to be 0.06 and 0.07, respectively. Absolute bioavailability from oral solution (10 mg) was 59 and 34%, and from tablets (8 mg) 44 and 25%, respectively, indicating extensive gut first-pass metabolism. Mean t _1/2 from 7 oral fasting studies in 5 subjects was 28 h (19–43 h). Mean absorption lag time was 0.7 h (0.4–1.3 h), and mean peak time was 2.8 h (2–4 h). In 2 subjects, 6 mg solutions were given every 12 h for 9 doses; good correlation between single and multiple dose kinetics was found. Significant accumulation was demonstrated in simulation studies with frequent daily dosing. Estimated accumulation ratios vary from 4.1 to 9.4 (mean 6.5). The t _1/2 from urinary data (collected for 12 days) was consistent with plasma data. The above results suggest the need to reexamine the current practice of frequent daily dosing and the use of sustained or controlled release dosage forms of this drug. The possible cause of reduced plasma clearance of CPM in renal patients is discussed.     

Pharmacokinetics of xamoterol after intravenous and oral administration to volunteers

Summary The pharmacokinetics of xamoterol, a -adrenoceptor partial agonist under clinical evaluation for the treatment of mild to moderate heart failure, have been studied in 12 healthy male subjects. They received 14 mg i.v. and oral doses of 50 and 200 mg as a tablet and 200 mg as a solution in a 4 way cross-over design.After i.v. dosing the elimination half-life was 7.7 h, the total body clearance was 224 ml·min^–1 and the volume of distribution at steady-state (V_ss) was 48 l. Sixty-two percent of the dose was recovered unchanged in urine. After oral doses, the absolute bioavailability of xamoterol was shown to be 5% irrespective of whether the dose was administered as a tablet or solution. Peak plasma concentrations occurred at about 2 h for the tablet dose and slightly earlier (1.4 h) for the solution. Peak plasma concentration, AUC and urinary recovery of unchanged drug increased in proportion to dose. The apparent elimination half-life after oral doses (16 h) was significantly longer than that observed after an intravenous dose.Despite the low bioavailability, the degree of inter-subject variability of oral bioavailability was small probably indicating that the controlling factor is the hydrophilic nature of the molecule rather than extensive first pass metabolism or poor dissolution of xamoterol from the tablet formulation.     

Pharmacokinetics of amiodarone after intravenous and oral administration

Summary Seven patients with cardiac arrhythmias were given amiodarone 400 mg intravenously over 2 min, and 2–4 days later the same dose was given orally. The serum concentration of amiodarone was determined by HPLC; the sensitivity of the analysis was 0.1 µg/ml. The time sequence of the measurements of drug concentration made conventional compartemental analysis impossible. There was large individual variation but some of the curves suggested enterohepatic circulation. The time from oral intake to the peak serum concentration was estimated to be 7.3±2.9 h (SD). The amount of drug reaching the general circulation in 24 h after oral intake averaged 42% (22–80%). After oral administration of amiodarone 200 mg 8 hourly the serum concentration before the morning dose averaged 0.61 µg/ml after 24 h, 0.76 after 48 h, 1.18 after 1 week and 1.56 µg/ml after 1 month. In one patient, who had been on amiodarone therapy for 8 months, the drug was discontinued and the serum concentration was followed over the next 3 months. The drug elimination curve suggested an elimination half life of 13.7 days. Because of instability in physiological saline protein binding could not be precisely quantitated, but only characterized as strong. No unchanged amiodarone was found in urine. The urinary excretion of iodine over 2 h after intravenous administration suggested that 5% of orally administered amiodarone was eliminated in the urine after biotransformation. No effect of the drug was observed during the first 10 days of treatment. In 2 patients with supraventricular arrhythmia, an excellent response was seen, and in one with ventricular arrhythmia there was a good response.     

Pharmacokinetics and bioavailability of intravenous,oral, and rectal nitrazepam in humans

The pharmacokinetics and bioavailability of nitrazepam following intravenous, oral (tablet), and rectal (solution) administration were studied in seven healthy, young male volunteers. Nitrazepam plasma concentrations were determined by electron-capture GLC; pharmacokinetic evaluations were made by compartmental analysis (NONLIN) and compared with the results obtained by a less stringent modelling of the data. The plasma concentration-time profile was similar for all three routes of administration. Mean kinetic parameters as obtained by compartmental analysis of i.v. nitrazepam were: distribution half-life 17 min; volume of distribution after equilibrium 2.14 liters/kg; total plasma clearance 61.6 ml/min; elimination half-life 29.0 h. The mean protein unbound fraction of nitrazepam in plasma was 12.3% and the clearance of the unbound fraction was 506 ml/min. Absorption of oral nitrazepam started after the elapse of a lag time (mean value 12 min) and occurred as an apparent first-order process in all but one subject, with a mean absorption half-life of 16 min. Distribution and elimination half-lives were comparable with those following i.v. administration. Following rectal administration of the nitrazepam solution, rapid first-order absorption occurred with a mean lag time of 4 min and a mean absorption half-life of 9 min. Peak times (median 18 min) were significantly shorter than following oral administration (median 38 min), but there was little difference in peak concentrations. The distribution half-life was similar to i.v. and oral administration, but the elimination half-lives were longer with a mean value of 33.1 h. Following i.v. administration a good agreement was found between the results obtained by compartmental analysis using NONLIN and those obtained by a less stringent modelling of the data. Following oral and rectal administration, a good agreement between the two procedures was found for the elimination half-life; estimation of bioavailability, however, was higher by compartmental analysis. The mean bioavailability data showed that absorption is complete when nitrazepam is given orally and almost 20% lower when it is given rectally, but considerable interindividual differences were observed.     

Pharmacokinetics of intravenous and oral tolmesoxide

Summary A high pressure liquid chromatographic assay was developed for simultaneous measurement of the plasma levels of tolmesoxide and its principal metabolite, RX71112. The assay was used to study the disposition of intravenous and oral tolmesoxide in ten normotensive subjects. Two exponential terms were required to describe the disposition of the drug following intravenous administration, whilst a single exponential term sufficied to account for the decay in the plasma concentration after oral administration. The bioavailability of oral tolmesoxide from capsules averaged 84.5% and was independent of dose. The mean half-life after i. v. dosing was 2.6 h (±0.3 SEM) compared to values of 1.9 h (±0.1 SEM) and 2.7 h (±0.5 SEM) following 200 and 400 mg oral doses respectively. In all subjects RX71112 appeared in plasma shortly after tolmesoxide following both routes of administration. The terminal half-life of the metabolite was significantly longer than tolmesoxide with a mean value of 4.9 h (±0.9 SEM) following the 200 mg oral dose of tolmesoxide. The binding of tolmesoxide and RX71112 at therapeutic plasma concentration was 36.8% (±0.5 SEM) and 58.5% (±0.3 SEM) and this remained unchanged at higher concentrations.     

Kinetics of cotinine after oral and intravenous administration to man

Summary Cotinine, the main metabolite of nicotine, was administered intravenously to healthy male non-smoking volunteers in doses of 5, 10 and 20 mg, and orally in doses of 10 and 20 mg.Intravenous administration was characterized by a dose-independent half-life of 12.2 h, mean residence time of 15.9 h, total clearance of 3.64 l h^–1 and a volume of distribution of 56.5 l. Renal clearance was 0.46 l h^–1 and approximately 12.0% of the dose was excreted unchanged in the urine. The mean absorption time after oral dosing ranged between 1 and 3 h, the peak concentration was reached within 45 min and the mean elimination half-lives were 12.9 and 11.7 h, respectively, after the 10 and 20 mg doses. Systemic bioavailability ranged between 0.84 and 1.11 following 10 mg and between 0.97 and 1.03 following the 20 mg dose. Mean urinary recovery and renal clearance were almost identical with the values after iv administration.     

Pharmacokinetics of midazolam in children: comparative study of intranasal and intravenous administration

Summary Twelve children 1–5 y old were randomly assigned to receive midazolam 0.2 mg·kg^–1 either by the intravenous (IV) or intranasal (IN) routes.After IN administration the rapid onset of absorption was observed (t_max 12 min). After both routes of administration the half-life was similar (2.2 h IN and 2.4 h IV). After IN administration the apparent plasma clearance and volume of distribution were about twice as high as after IV administration.The results are consistent with an estimated mean bioavailability of 55%.     

Pharmacokinetics of the new analgesic,meptazinol, after oral and intravenous administration to volunteers

Summary The pharmacokinetics of meptazinol (Meptid^®) have been studied in nine male volunteers after single and multiple oral administration of 200 mg tablets and also after a single 25 mg intravenous dose. Plasma concentrations of meptazinol were determined by HPLC using fluorescence detection. Drug absorption after oral dosage was rapid, peak plasma concentrations being reached between 0.25 and 2 h after drug administration. Subsequent elimination proceeded in an apparently mono-exponential fashion with a half-life of 2 h, although after intravenous dosage there was evidence of an initial rapid distributive phase. The mean total plasma clearance was 2.21/min and the mean apparent volume of distribution (Vd) was 4.99 l/min. The bioavailability ranged from 1.9 to 18.5% (mean=8.7%) and was related to the rate of absorption. Multiple dosing, 6-hourly for 3 days, did not produce any accumulation above that predicted from a single dose. Plasma protein binding of the drug was 27.1% and did not vary over the therapeutic concentration range of 25 to 250 ng/ml.     

Pharmacokinetics of reboxetine in healthy volunteers. Single oral doses,linearity and plasma protein binding

The pharmacokinetics of reboxetine, a new antidepressant agent, were found to be close to linear in a crossover study comparing administration of single 2, 3, 4 and 5 mg capsule doses in 15 healthy male volunteers, and in the same study the capsules were bioequivalent to the proposed therapeutic tablet formulation (4mg). Kinetic analysis was based on HPLC assay of reboxetine in plasma and urine collected up to 72 h after each administration. Plasma levels indicated a rapid absorption (t_max?2h) and an elimination half-life of about 13 h. Clearance and volume of distribution were modest (ratios to bioavailability: CL/F?29 mL min^?1; V_z/F?32L); urinary excretion was ～9% of dose, corresponding to a renal clearance of only 3 mL min^?1 (a value consistent with the rate of glomerular filtration of unbound drug). In vitro, binding to plasma proteins, estimated from radioactivity levels following dialysis of ¹⁴C-labelled reboxetine, appeared to be dominated by α₁-acid glycoprotein without marked saturation up to plasma concentrations of over 500 ng mL^?1 (2.8–3.1% unbound with human plasma from three additional volunteers; 1.8–2.0% for 2gL^?1 orosomucoid α₁-acid glycoprotein, and 46.4–47.4% for 40 gL^?1 albumin), whilst the mean C_max in the current study was much lower (164 ng mL^?1 after a 5 mg dose).     

A Stochastic Model Describes the Heterogeneous Pharmacokinetics of Cyclosporin

The pharmacokinetics of cyclosporin (CsA) are unusual because of several heterogeneous features which include the presence of more than one conformer, considerable accumulation in erythrocytes and lipoproteins, extensive plasma protein binding, distribution into deep tissues, biliary secretion and hepatic clearance involving a large number of metabolites. In this study, a stochastic compartmental model was developed to describe the heterogeneous elimination kinetics of CsA. This new approach relies on a probabilistic transfer model with a gamma distributed probability intensity coefficient for drug elimination. For comparative purposes both the stochastic model and compartmental deterministic models were fitted to real post infusion data from patients receiving CsA as a 2-hr intravenous infusion. The criteria for selecting the best model showed that the stochastic model, although simpler than the compartmental deterministic models, is more flexible and gives a better fit to the kinetic data of CsA than the compartmental deterministic models. The stochastic model with a random rate intensity coefficient adequately describes the heterogeneous pharmacokinetics of CsA.     

Pharmacokinetics of ketanserin and its metabolite ketanserin-ol in man after intravenous,intramuscular and oral administration

Summary The pharmacokinetics of ketanserin (R 41468), a novel serotonin S₂-receptor blocking agent widely investigated for its effect on acute and chronic hypertension, has been studied in 10 healthy male subjects. They received single 10 mg doses i.v. and i.m., and 20, 40 and 60 mg solutions of ketanserin by mouth, in a five-way cross-over design. The model-independent kinetics of i.v. ketanserin were characterized by a terminal half-life of 14.3±4.4 h, a moderate plasma clearance (CL=565±57 ml/min) and a large tissue distribution (V_ss=268±71 l, V_z=703±204 l; mean ± SD). Following i.m. administration, peak levels of nearly 200 ng/ml were attained within 10 minutes and the absolute bioavailability was 112±23%. After oral dosing, peak levels of ketanserin were reached within 1 h. The peak level and AUC increased in proportion to the dose. The absolute bioavailability was 46.8, 50.4 and 55.5% for 20, 40 and 60 mg doses and they conformed to the predicted bioavailability based on i.v. clearance data. The terminal half-life of 17 h and the urinary excretion of parent drug (about 0.7% of the dose) were similar after oral and parenteral dosing. The kinetics of ketanserin-ol, the major metabolite of ketanserin formed by ketone reduction, was also studied. Because of its negligible pharmacological activity, the contribution of ketanserin-ol to the overall therapeutic effect of ketanserin is small, in spite of its 1.6-times (parenteral) to 3.2-times (oral) higher plasma level than that of ketanserin. The particular role of the metabolite is discussed in the light of the clinical pharmacokinetics of ketanserin.     

Pharmacokinetics of metformin after intravenous and oral administration to man

Summary The kinetics of¹⁴C-metformin have been studied in five healthy subjects after oral and intravenous administration. The intravenous dose was distributed to a small central compartment of 9.9±1.61 ( ±SE), from which its elimination could be described using three-compartment open model. The elimination half-life from plasma was 1.7±0.1 h. Urinary excretion data revealed a quantitatively minor terminal elimination phase with a half-life of 8.9±0.7 h. After the intravenous dose, metformin was completely excreted unchanged in urine with a renal clearance of 454±47 ml/min. Metformin was not bound to plasma proteins. The concentration of metformin in saliva was considerably lower than in plasma and declined more slowly. The bioavailability of metformin tablets averaged 50–60%. The rate of absorption was slower than that of elimination, which resulted in a plasma concentration profile of flip-flop type for oral metformin.     

Pharmacokinetics of xamoterol after intravenous and oral administration to patients with chronic heart failure

Summary The pharmacokinetics of xamoterol, a -adrenergic partial agonist under clinical evaluation for the treatment of mild to moderate heart failure, have been studied in 8 cardiac failure patients (NYHA Class II) of mean age 62 years.After i.v. dosing, the elimination half-life was 7.4±0.4 h, the total body clearance was 228±30 ml·min^–1 and the volume of distribution at steady-state was 56±91. 72.5±4.3% of the dose was recovered unchanged in urine. After the oral dose, the absolute bioavailability of xamoterol was shown to be 5.9%. Peak plasma concentrations occurred 1 to 2.5 h after the oral dose. The apparent elimination half-life was significantly longer after oral doses (16±2 h) compared to that observed after an intravenous dose. Renal clearance of xamoterol exceeded glomerular filtration rate as measured by creatinine clearance.The pharmacokinetics of xamoterol in cardiac failure patients with good renal function (creatinine clearance >90 ml·min^–1) were similar to published data in young healthy male volunteers.     

Pharmacokinetics,metabolism, excretion and plasma protein binding of 14C-levofloxacin after a single oral administration in the Rhesus monkey

Levofloxacin's metabolism, excretion, and in vitro plasma protein binding, together with its pharmacokinetics, were studied in the Rhesus monkey in support of an anthrax efficacy study in this species. Three males and three female Rhesus monkeys were dosed with a single oral dose of ¹⁴C-levofloxacin at 15?mg?kg^?1 (2?MBq?kg^?1). Following dose administration, blood samples were collected up to 48?h post-dose, and urine and faeces were quantitatively collected up to 168?h post-dose. Blood, plasma, urine, and faeces were analysed for total radioactivity. Metabolite profiling and identification was performed using radio-high-performance liquid chromatography (HPLC) and liquid chromatography coupled with tandem mass spectrometry detection (LC-MS/MS). Additionally, the plasma protein binding of levofloxacin was determined in vitro by means of equilibrium dialysis. Peak plasma levels of total radioactivity and levofloxacin were rapidly reached after oral administration with a total radioactivity blood: plasma ratio close to unity. The elimination half-life of levofloxacin was estimated at about 2?h. Total radioactivity was mainly excreted in urine (about 57–86% of the dose) with faecal excretion accounting for only a minor fraction of the total amount of excreted radioactivity (about 7.4–14.7%). In the plasma, the majority of total radioactivity was accounted for by levofloxacin. In addition, two minor metabolites, i.e. levofloxacin n-oxide and presumably a glucuronide conjugate of levofloxacin, were detected. In the urine, five components were found, with levofloxacin being the major component. Minor metabolites included desmethyl levofloxacin, levofloxacin n-oxide, and a glucuronide conjugate of levofloxacin. In the faeces, the major analyte was a polar metabolite, tentatively identified as a levofloxacin glucuronide. The in vitro plasma protein binding was low (on average 11.2%) and independent of concentration (1.0–10.0?µg?ml^?1). No sex differences were noted in any of the investigations. The present data indicated that the metabolism and excretion pattern, and also the in vitro plasma protein binding of levofloxacin in the Rhesus monkey, were comparable with those previously reported in man, hereby supporting the use of this animal species in the efficacy evaluation of levofloxacin against inhalation anthrax. The shorter half-life of levofloxacin in the Rhesus monkey relative to man (2 versus 7?h) prompted the development of an alternative dosing strategy for use in the efficacy study.     

Pharmacokinetics and tissue distribution of chlorpheniramine in rabbits after intravenous administration

Intravenous studies of chlorpheniramine (CPM) were conducted in six New Zealand White male rabbits (mean wt. 3.88 kg). CPM and its two demethylated metabolites in arterial serum and urine were assayed by HPLC. Triexponential equations were needed to fit the i.V. CPM serum data in three rabbits, while biexponential equations were required in the other three rabbits. Harmonic mean of V₁, V_ss, V _area , CL,and terminal t _1/2 were 2.84, 10.8, and 15.5 liters/kg, and 4.14 liters/kg/hr and 2.57 hr, respectively. The average serum protein binding was 44%. The average blood to plasma concentration ratio was 1.85. Estimated mean hepatic blood extraction ratio based on i.v. studies was 0.88. Tissue distribution studies showed rapid and extensive uptake of CPM by various organs such as lung, kidneys, and brain after i.v. bolus injection, as their concentrations were 160-, 80-, and 31- fold higher than the plasma level. The amount of CPM in the muscle was calculated to represent about 50% of CPM present in the body near the steady state. Variation in plasma protein and tissue binding was postulated to be an important factor for the observed marked interspecies difference in the apparent volume of distribution of CPM. Only 2% of the dose was excreted unchanged in the urine.     

Pharmacokinetics of bolus intravenous and oral doses of L-carnitine in healthy subjects

Summary The pharmacokinetics of single intravenous and oral doses of L-carnitine 2 and 6 g was studied in 6 healthy subjects on a low-carnitine diet. Carnitine was more rapidly eliminated from plasma after the 6 g dose. Comparing the doses, the t_1/2 of the elimination phase () was 6.5 h vs 3.9 h, the elimination constant 0.40 vs 0.50 h^–1 and the plasma carnitine clearance was 5.4 vs 6.11 · h^–1 for the 2 g and 6 g doses, respectively, showing dose-related elimination. Saturable kinetics were not found. The apparent volumes of distribution after the two doses were not significantly different and were of the same order as the total body water. Urinary recoveries of the 2 g and 6 g doses were 70% and 82%, respectively, during the first 24 h. Following the oral doses, there was no significant difference between the areas under the plasma carnitine concentration-time curves. Urinary recovery was 8% and 4% for the 2 g and 6 g doses during the first 24 h. Oral bioavailability was 16% for the 2 g dose and 5% for the 6 g dose. The results suggest that the mucosal absorption of carnitine was already saturated by the 2 g dose.