Pharmacokinetics of ciprofloxacin in healthy volunteers after oral and intravenous administration

The pharmacokinetics of ciprofloxacin was studied in three groups of healthy volunteers comprising a total of 16 males and 16 females (age 21–35 years; body weight 52–80 kg). Single oral doses of 50, 100, 250, 500 and 750 mg were given to fasting subjects. The 250 mg dose was repeated after a breakfast. Intravenous doses of 50, 100 and 200 mg were given by short infusion in a randomized cross-over sequence. Concentrations of the drug in serum and urine were determined by high-performance liquid chromatography and by a microbiological assay. Mean peak concentrations between 0.37±0.49 mg/l (100 mg dose) and 1.97±0.50 (750 mg dose) were measured 60–75 min after oral administration. Twelve hours after 750 mg ciprofloxacin, serum concentrations were 0.15±0.05 mg/l. Taking a breakfast reduced absorption by 15–20% compared to the fasting state, as judged by peak concentrations, AUC and renal excretion. After 200 mg i. v. (20 min infusion period), initial serum concentrations of 4.0±1.2 mg/l were observed which declined 12 h later to 0.070±0.025 mg/l. Mean cumulated recovery of ciprofloxacin from urine over 24 h varied between 25.5% and 33.6% of oral doses and between 53.2% and 57.4% of intravenous doses. Two of the three metabolites seen in the chromatograms were identified as M1 and M3 (oxo-ciprofloxacin). Cumulated renal excretion after an oral 250 mg dose was 1.2±0.4% of M1 and 5.5±1.6% of M3. Bioavailability of oral doses varied from 0.64±0.16 (100 mg) to 0.52±0.11 (500 mg). The AUC was linearly proportional to a single dose of up to 250 mg. Ciprofloxacin was rapidly absorbed and distributed. High distribution volumes were calculated (mean VD_area 186–217 1). The terminal half-life (t₁/2) was 3.1 to 5.4 h. Mean total body clearance was also high (600 to 693 ml/min · 70 kg)). Tolerance of ciprofloxacin was good for all oral doses and for intravenous administration up to 100 mg per dose. Intravenous infusion of 200 mg ciprofloxacin caused transient local irritation.     

Tissue penetration and pharmacokinetics of lomefloxacin following multiple doses

The pharmacokinetics of lomefloxacin were studied after three days of oral administration of 400 mg/day lomefloxacin. Following the final dose the concentrations in serum, urine and cantharidin-induced inflammatory fluid were measured by a microbiological assay. The mean peak serum level was 4.9 mg/l at a mean time of 0.8 h. The mean serum elimination half-life was 6.2 h. The mean maximum inflammatory fluid level attained was 3.2 mg/l at 2.7 h. Urinary recovery accounted for the greater part of lome-floxacin's elimination.     

Effects of propranolol on the pharmacokinetics of cyclosporine after intravenous and oral administration to control rats and rats with uranyl nitrate-induced acute renal failure.

Effects of propranolol on the pharmacokinetics of cyclosporine were investigated after intravenous and oral administration of the drugs to control rats and rats with uranyl nitrate-induced acute renal failure (U-ARF). Effects of intravenous propranolol, 3 mg/kg, on the pharmacokinetics of intravenous cyclosporine, 3 and 30 mg/kg, to control rats, and 30 mg/kg, to rats with U-ARF seemed to be negligible. However, the effects of orally administered propranolol, 10 mg/kg, on the area under the blood concentration-time curve (AUC) of oral cyclosporine were significant after oral administration of cyclosporine, 10 and 100 mg/kg, to control rats. For example, the AUC of cyclosporine increased significantly (33.1 versus 24.7 microg h/ml) at cyclosporine oral dose of 10 mg/kg, however, the value decreased significantly (167 versus 235 microg h/ml) at cyclosporine oral dose of 100 mg/kg. Effects of orally administered propranolol, 10 mg/kg, on the pharmacokinetics of orally administered cyclosporine, 100 mg/kg, seemed to be negligible in rats with U-ARF.     

Ketoconazole pharmacokinetics during chronic dosing in adults with haematological malignancy

Ketoconazole pharmacokinetics were determined in nine adults with haematological malignancy after one week on a 200 mg daily dose and later after one week on a 400 mg daily dose. The area under the serum concentration time curve (AUC) reached 12.3 ± 7.7 mg/l.h (mean ± S.D.) on the 200 mg dose and increased to 23.0 ± 18.2 mg/l.h on the 400 mg dose (p < 0.05). The half-life of ketoconazole was 3.1 + 1.9 h on the 200 mg dose and 3.5 ± 1.7 h on the 400 mg dose. Peak concentrations were 3.2 ±1.8 mg/l and 4.6 ± 3.2 mg/l on the 200 mg and 400 mg doses, respectively. Trough ketoconazole concentrations were undetectable 24 h after either dose. There was no correlation between the leucocyte count and any pharmacokinetic parameter for ketoconazole. Variation in AUC was 20-fold on the 200 mg daily dose and 8-fold on the 400 mg per day regimen. Measurement of serum levels during ketoconazole treatment appears necessary in view of the unpredictable concentrations achieved. Once-a-day dosage regimens of ketoconazole in immunocompromised patients may be inappropriate. Future clinical trials should adopt a two or three times a day dosing regimen, as this may confer a pharmacokinetic and therapeutic advantage.     

Pharmacokinetics of oral and intravenous rifampicin during chronic administration

Summary We investigated the pharmacokinetics of rifampicin and its major metabolites, 25-desacetylrifampicin and 3-formylrifampicin, in two groups of six patients with active pulmonary tuberculosis, who received either multiple oral or intravenous rifampicin therapy in combination with intravenous isoniazid and ethambutol. Serum concentrations of rifampicin were each determined after a single oral and intravenous test dose of 600 mg rifampicin at the beginning and after 1 and 3 weeks of tuberculostatic treatment. Analysis of rifampicin and its metabolites was performed by high-pressure liquid chromatography. It was found that, due to autoinduction of its metabolizing hepatic enzymes, the systemic clearance of rifampicin increased from 5.69 to 9.03 l/h after 3 weeks of multiple dosing. The volume of distribution of the drug was constant over the period of this study. The bioavailability of the active, orally administered rifampicin decreased from 93% after the first single oral dose to 68% after 3 weeks of oral and intravenous rifampicin therapy. Relating to the increase in systemic (hepatic) clearance, a bioavailability no lower than 90% can be predicted. The reduction to 68% indicates that, in addition to an increase of hepatic metabolism, an induction of a prehepatic first-pass effect resulted from multiple rifampicin doses. Our study of rifampicin metabolites confirm that prehepatic metabolism was induced, since a higher metabolic ratio resulted after the oral doses than after the intravenous rifampicin test doses. A preabsorptive process can therefore be excluded as a cause of reduced bioavailability.Abbreviations AUC area under the serum concentration-time curve - Cl clearance - RMP rifampicin - t 1/2 half-life - Vd_area volume of distribution Dedicated to Professor Dr. Hans J. Dengler on the occasion of his 60th birthday     

Pharmacokinetics of ciprofloxacin after oral and intravenous administration in healthy volunteers

The pharmacokinetics of ciprofloxacin (Bay o 9867) was examined after a single oral dose of 250 mg and a single intravenous dose of 100 mg respectively in six healthy male volunteers in an open, randomized crossover study. Although ciprofloxacin concentrations were measured in serum, plasma and urine by HPLC with fluorimetric detection and by microbiological assay, all pharmacokinetic calculations are based on the highly sensitive HPLC method only. The mean serum concentration of ciprofloxacin peaked approximately1 h after the oral dose (0.94 mg/l). The elimination half-life was about 4 h and the renal clearance was 4.75 ml/min·kg; both were independent of the route of administration. The total clearance (9.62 ml/min·kg) was about twofold higher than the renal clearance. The volume of distribution of the central compartment was calculated to be 0.16 l/kg and the total volume at steady state was 2.0 l/kg. About 27 % of the oral dose was excreted in urine, whereas the urinary recovery of the i.v. dose was 46 %. The absolute bioavailability of ciprofloxacin was found to be approximately 60 %. Ciprofloxacin appears to follow first-order, three compartment model kinetics.     

Pharmacokinetics of roxithromycin and influence of H2-blockers and antacids on gastrointestinal absorption

The pharmacokinetics of roxithromycin (300 mg orally) and the influence of the antacid aluminum magnesium hydroxide and the H₂-blocker ranitidine on bioavailability of roxithromycin in ten healthy volunteers were studied. Pharmacokinetics after a single dose of roxithromycin were characterized by high peak serum levels (9.1 ± 2.1 mg/l) and a long elimination half-life (7.2 ± 2.5 h), resulting in a large area under the curve (116.9 ± 32.7 mg h/l). High inter- and intraindividual variations were found for both the absorption time and the elimination half-life. The bioavailability of roxithromycin was not affected by coadministration with antacids or ranitidine.     

Desmethyldiazepam kinetics after intravenous,intramuscular, and oral administration of clorazepate dipotassium

Summary The pharmacokinetics and bioavailability of desmethyldiazepam (DMDZ), formed from its precursor clorazepate (CZP) dipotassium, were assessed in a series of 17 healthy volunteers aged 21–66 years. After a single 20-mg intravenous dose of CZP, mean kinetic variables for DMDZ were: volume of distribution, 1.24 l/kg; elimination half-life, 65 h; total clearance, 0.24 ml/min/kg. Among males, DMDZ half-life tended to be prolonged and clearance reduced with age, but this was not true for females. After oral administration of 20 mg CZP, appearance of DMDZ in the circulation was rapid; the mean peak plasma level was 356 ng/ml, reached an average of 0.9 h after dosage. Based on comparison with IV dosage, systemic availability of DMDZ was complete (100% absorption). Ten of the subjects also received a single 20-mg intramuscular dose of CZP. Mean peak DMDZ levels were 290 ng/ml, reaching an average of 2.7 h after dosage. Systemic availability of DMDZ was complete. Elimination half-life of DMDZ for a given individual was highly replicable from trial to trial regardless of the route of CZP administration.Part of doctoral thesis E. Steinhaus, University of Bonn 1982     

Pharmacokinetics of ciprofloxacin in the elderly: Increased oral bioavailability and reduced renal clearance

The pharmacokinetics of ciprofloxacin was studied after single intravenous and oral doses of 250 mg and during and after a five-day oral regimen of 500 mg twice daily in eight young (22–34 years) and eight elderly (63–76 years), healthy male volunteers. The absolute bioavailability of an oral dose was greater in the elderly than in the young subjects at both 250 mg (72 versus 58 %; p<0.05) and 500 mg (79 versus 63 %; p<0.05). Distribution was unaffected by age. The physiological aging of the kidneys resulted in a reduced renal clearance, while no significant changes in non-renal clearance, total clearance and terminal half-life were found in the elderly. The age-related increase in the bioavailability of ciprofloxacin, whether due to facilitated absorption and/or reduced first-pass elimination, is a hitherto unique finding for antibiotics. As a consequence, reduction of orally administered doses of ciprofloxacin should be considered for elderly patients.     

Concentrations of azithromycin in human tonsillar tissue

Patients scheduled to undergo tonsillectomy were administered 500 mg oral azithromycin as two 250 mg capsules given 12 h apart. Between 9 h and one week after the second dose, tonsil samples were taken during surgery and assayed for azithromycin. Mean concentrations in tonsillar tissue, 12 and 24 h after the second of the two 250 mg doses given 12 h apart, were 4.5 and 3.9 µg/g, respectively. Concurrent mean serum concentrations were approximately 0.03 and 0.01 µg/ml, respectively. The mean concentration in tonsillar tissue 7.5 days after the last dose was 0.93 µg/g. The apparent half-life of drug in the tissue was 76 h. The ratio of mean concentration in tissue to that in serum was greater than 150-fold for all time intervals. The presence of high azithromycin concentrations in tonsillar tissue suggests that a once-daily regimen over five days or less may be effective in treating tonsillo-pharyngitis.     

Pharmacokinetics and tissue penetration of single-dose netilmicin used for antibiotic prophylaxis during colo-rectal surgery

Pharmacokinetics and tissue penetration of netilmicin were studied after the use of a single dose (6 mg/kg) given for antibioprophylaxis in colo-rectal surgery. Thirteen patients, scheduled for elective surgery, were given 6 mg/kg IV netilmicin over 30 min, together with 1000 mg IV ornidazole. Netilmicin peak serum concentration (10 min after end of infusion) was 24.4 +/- 3.4 mg/l and trough level (24 h) was 0.9 +/- 0.5 mg/l. Plasma elimination half-life was 409 +/- 70 min, le volume apparent volume of distribution was 38 +/- 101 and total body clearance was 0.07 +/- 0.02 ml/min. Adequate netilmicin levels (5 greater than or equal to CMI 90 of involved pathogens Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus) were obtained in 100 per cent of patients in abdominal wall and epiploid fat, at time of opening, and in colonic wall at time of anastomosis. Adequate levels were obtained at time of closure in abdominal wall and epiploid fat in 92 to 100 per cent of patients. In situation of allergy to beta-lactam antibiotics, the use of netilmicin in combination with ornidazole may be recommended.     

Nifedipine: Kinetics and dynamics after single oral doses

Summary Serum nifedipine concentrations and hemodynamic changes were evaluated in ten healthy volunteers after a single 40-mg oral dose of nifedipine. Peak serum concentrations averaged 45 µg/l, attained 2.7 h after dosage. The mean elimination half-life was 5.9 h (range: 3–12 h). Blood pressure, ventricular rate, and echocardiographically-determined rate of circumferential fiber shortening did not differ between placebo and nifedipine trials. Five additional subjects ingested nifedipine once in the control state and on a second occasion with a standard breakfast. Coingestion of food delayed the peak serum nifedipine concentration but did not alter the area under the serum concentration curve. Thus the pharmacokinetic profile of nifedipine indicates that a three- or four-times-daily dose is, in general, appropriate in clinical practice. Completeness of absorption is not altered by coadministration with food. Adverse hemodynamic effects of single oral doses in healthy persons are not evident.Supported in part by Grant Oc 10/6-4 from Deutsche Forschungsgemeinschaft     

Influence of beta-blocker coadministration on the kinetics of isosorbide mononitrate and dinitrate

Summary The influence of beta-blocker coadministration on the kinetics of oral isosorbide-5-mononitrate (ISMN) and isosorbide dinitrate (ISDN) was studied in healthy volunteers. In the first study, 12 subjects ingested 20 mg ISMN on three occasions in the control state, during coadministration of metipranolol (20 mg 3 times daily), or during metoprolol (100 mg twice daily). There were no significant differences among the three phases in peak serum ISMN concentration (470 ng/ml), the time of peak (0.6 h after dose), elimination half-life (4.5 h), or oral clearance (142 ml/min). In the second study, 10 subjects received 20 mg ISDN in the control state and again during coadministration of propranolol (80 mg 3 times daily). There were no differences between the two phases in peak serum ISDN concentration (20 ng/ml) or the time of peak (0.6 h). Propranolol increased, although not significantly, ISDN clearance (16.5 vs 12.3 L/min,P<0.1), and had no effect on total area under the curve for ISMN, the major metabolite of ISDN. Thus, therapeutic doses of these beta-blockers have a minimal influence on the kinetics of single doses of ISMN or ISDN in healthy individuals.Abbreviations AUC Area under curve - ISDN Isosorbide dinitrate - ISMN Isosorbide-5-mononitrate Supported in part by grant OC 10/6-4 from the Deutsche Forschungsgemeinschaft, and a grant from Boehringer Mannheim, Federal Republic of Germany     

Single- and multiple-dose administration, dosing regimens, and pharmacokinetics of trovafloxacin and alatrofloxacin in humans

A simplified dosing algorithm for trovafloxacin was evaluated following a single-dose infusion of alatrofloxacin at trovafloxacin equivalent doses of 30, 100, 200, 300 and 400 mg (57 subjects), and multiple doses of 200, 300 and 400 mg (30 subjects). Maximum serum concentration and area under the concentration-time curve for trovafloxacin increased with dose. Trovafloxacin clearance (82–85 ml · h/kg) and volume of distribution (1.3–1.6 l/kg) were independent of dose. Infusion of alatrofloxacin at a trovafloxacin equivalent dose of 300 mg at 1, 2 or 3 mg/ml over 1 h did not alter the pharmacokinetics of trovafloxacin. A plot of the weight-adjusted dose of trovafloxacin in individual subjects against the maximum serum concentration following single and multiple dosing, indicated that the maximum serum concentration increased 1 g/ml for each 1 mg/kg of trovafloxacin administered. Thus, a prior knowledge of the desired serum concentration will permit appropriate dosing without the use of complex nomograms in patients with normal hepatic function.     

Allergic asthma and an anti-CD23 mAb (IDEC-152): results of a phase I,single-dose,dose-escalating clinical trial

BACKGROUND: CD23, a cell-surface molecule, is involved in a variety of pathways likely to influence IgE production and inflammation in allergic disorders, such as allergic rhinitis and allergic asthma. OBJECTIVE: This study investigated the safety, clinical activity, and pharmacokinetic profile of IDEC-152, an IgG1 anti-CD23 antibody, in patients with mild-to-moderate persistent allergic asthma. METHODS: This single-dose, dose-escalating, placebo-controlled study involved 30 patients. Cohorts of 3 to 6 patients received single intravenous infusions of either placebo or IDEC-152 (0.05, 0.25, 1.0, 4.0, 10.0, or 15.0 mg/kg) on study day 1. Safety, clinical activity, and pharmacokinetics were assessed for 12 weeks after treatment. RESULTS: IDEC-152 was well tolerated. Adverse events (AEs) were mild, no grade 4 or serious AEs were reported, and no relationships were apparent between the dose of IDEC-152 and the frequency, severity, or type of event. The most common AEs in the IDEC-152 group included ecchymosis at the injection site, sinusitis, headache, arthralgia, cold syndrome, infection, throat irritation, and dysmenorrhea. Commonly reported AEs in the placebo group included headache, abdominal pain, and infection. Sustained and dose-dependent decreases in mean IgE concentrations were noted. The mean maximum concentration and area under the curve of IDEC-152 were proportional to the dose administered for the dose range 4.0 to 15.0 mg/kg. The serum half-life of the IDEC-152 antibody increased from 2 to 10 days with increasing doses. After single-dose administration of IDEC-152, no dose-dependent change in FEV(1) was observed, and most changes in peak expiratory flow rate were within 10% of baseline values. CONCLUSION: These data suggest that IDEC-152 is safe and has the potential for clinical activity in allergic asthma.     

Alterations in the half-life and clearance of IgG during therapy with intravenous γ-globulin in 16 patients with severe primary humoral immunodeficiency

Published studies of the metabolism of human IgG using trace amounts of radiolabeled IgG demonstrated that the elimination of native IgG followed first-order kinetics but that the half-life of IgG was shortest in patients with the highest serum concentrations of IgG. To evaluate the effect of increasing the serum concentration of IgG on the metabolism of IgG, we determined the half-life and clearance of IgG and tetanus antibody in 16 patients with severe primary humoral immunodeficiency diseases while they received several doses of intravenous -globulin (IVIG). Each patient received 100 mg/kg of IVIG each month and the half-life and clearance of IVIG were determined by following the decline in the serum IgG concentration. The dose of IVIG was adjusted to give a minimum IgG level of 200 mg/dl and the half-life was reevaluated. The dose was again adjusted to give minimum concentrations of 450 mg/dl and two additional studies were performed. Mean doses of IVIG infused increased from 100 to 346 mg/kg. The mean trough serum IgG concentration was 191 mg/dl on the standard dose and increased to 427 mg/dl at the highest dose. The serum half-lives of IgG were highly variable, ranging from 22 to 96 days. The mean decreased from 43 days in the first to 33 days in the third and fourth studies, and the clearances of IgG increased from 1.8339 to 2.4302 mg/kg/day, but the differences were not statistically significant. Patients with the highest serum IgG concentrations tended to have the longest half-lives, suggesting that intrinsic IgG production might falsely prolong the calculated half-life of IgG. However, it was possible to determine the half-life in these patients by measuring the decline in tetanus antibody. The half-life measured by this technique in the third and fourth studies was 27 and 36 days and the clearances were 2.988 and 3.648 ml/kg/day. Knowledge of the metabolism of IgG in these patients may lead to more appropriate guidelines for determination of dosage.     

Hepatobiliary elimination of trovafloxacin and metabolites following single oral doses in healthy volunteers

Trovafloxacin, a fluoronaphthyridone derivative related to fluoroquinolones, has significant activity against gram-negative and gram-positive pathogens, including penicillin-resistantStreptococcus pneumoniae, anaerobes and atypical organisms, good tissue penetration and a long elimination half-life. Following oral administration, less than 10% of the dose is renally eliminated as unchanged drug. Hepatobiliary elimination of trovafloxacin was examined by comparing the time course and bile and serum concentrations of trovafloxacin and its metabolites following oral administration to three patients with in-dwelling nasobiliary catheters or T-tubes. Following a single 200 mg oral dose, the mean maximum plasma trovafloxacin concentration was 2.0±0.4mg/l, the area under the concentration-time curve 22.0±5.5 mg·h/l and the elimination half-life 8.5 h. Values in bile for the same subjects were 27.8±9.6 mg/l, 327.7±142.9 mg·h/l and 10.7 h. Corresponding values for the N-acetyl metabolite in bile were 3.8±3.4 mg/l, 35.3±29.8 mg·h/l and 8.3 h. The mean bile : serum ratio of trovafloxacin was 149 and consistent with biliary elimination. Serum concentrations of trovafloxacin in this study were similar to those reported in healthy volunteers. Bile concentrations of trovafloxacin substantially exceeded those of theN-acetyl metabolite, suggesting efficient clearance of the metabolite or that hepatic metabolism of trovafloxacin is not extensive.     

Kinetics and cardiac effects of propranolol in humans

Summary Six healthy volunteers received single 20-mg intravenous (IV) and 80-mg oral doses of propranolol on two occasions in random sequence. Serum propranolol concentrations were determined by gas chromatography in multiple samples drawn during 24 h after each dose. Mean (±SE) kinetic variables for IV propranolol were: elimination half-life (t1/2), 5.3 (±0.6) h; volume of distribution, 2.3 (±0.3) l/kg; total clearance, 4.9 (±0.3) ml/min/kg; predicted extraction ratio, 0.23 (±0.02). After single oral doses, t1/2 (3.8±0.2 h) tended to be smaller than after the IV dose, and actual systemic availability (0.60±0.07) was less than that based on the predicted extraction ratio. During multiple oral dosage (80 mg every 12 h), observed steady state serum levels (47±5 ng/ml) tended to be less than those predicted based on the single oral dose (61±5 ng/ml), thus providing no evidence for reduced propranolol clearance at steady-state. Echocardiographic measurements of left ventricular performance (posterior wall velocity, diastolic dimensions) made during the single-dose oral study indicated significant impairment of function; impairment was maximal at 3 h post-dosage, and corresponded to the time of the peak serum propranolol concentration (341 ng/ml).Supported in part by Grant Oc 10/6-3 from Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg, FRG; and by Grant MH-34223 from the United States Public Health Service     

Ceftibuten concentrations in human tonsillar tissue

In a study designed to determine ceftibuten concentrations in tonsillar tissue, subjects scheduled to undergo tonsillectomy were administered 400 mg of ceftibuten in a single oral dose. Between 2 and 24 h after the dose was given, tonsillar tissue samples were taken during surgery and assayed for ceftibuten. Mean concentrations in tonsillar tissue 4.4 h and 24.6 h after the 400 mg dose were 5.3±2.7 and 0.3±0.3 mg/g, respectively. Concurrent mean serum concentrations were 7.42±1.66 and 0.15±0.13 mg/ml, respectively. The apparent half-life of drug in the tissue was 5.3 h. The presence of high ceftibuten concentrations in tonsillar tissue suggests that a once-daily regimen may be effective in treating tonsillitis and pharyngitis.     

Metabolism of D-ribose administered continuously to healthy persons and to patients with myoadenylate deaminase deficiency

Summary D-ribose was administered orally or intravenously over at least 5 h to eight healthy volunteers and five patients with myoadenylate deaminase deficiency. Intravenous administration rates were 83, 167, and 222 mg/kg/h, which were well tolerated but oral administration of more than 200 mg/kg/h caused diarrhea. The average steady state serum ribose level ranged between 4.8 mg/100 ml (83 mg/kg/h, oral administration) and 81.7 mg/100 ml (222 mg/kg/h, intravenous administration). Serum glucose level decreased during ribose administration. The intestinal absorption rate of orally administered ribose was 87.8%–99.8% of the intake at doses up to 200 mg/kg/h without first pass effect. Urinary losses were 23% of the intravenously administered dose at 222 mg/kg/h. Ribose appeared to be excreted by glomerular filtration without active reabsorption; a renal threshold could not be demonstrated. The amount of ribose transported back from the tubular lumen depended on the serum ribose level. There was no difference in ribose turnover in healthy subjects and patients with MAD deficiency.Abbreviations MAD myoadenylate deaminase - i.v. intravenous(ly)