Serum Elimination Half-life Research Articles

Apparent Reduced Absorption of Gemfibrozil When Given with Colestipol

Colestipol and gemfibrozil may be used in combination to lower serum cholesterol and triglycerides. Since colestipol is known to bind certain anionic drugs, we studied the effect of colestipol on the pharmacokinetics of gemfibrozil in 10 patients with elevated serum cholesterol and triglycerides. Each patient received 600 mg of gemfibrozil by mouth during four different studies. Gemfibrozil was given randomly either alone, with, 2 hours before, or 2 hours after 5 grams of colestipol. The serum gemfibrozil concentration time curves were similar when gemfibrozil was given alone or two hours before or after colestipol. There was also no statistical difference in peak gemfibrozil concentration (Cmax), time to Cmax (tmax), area under the curve (AUC), or serum elimination half-life (t1/2) between any of these three treatments. However, when colestipol was given with gemfibrozil, there was a decrease in AUC (43.6 +/- 21.9 mg*hr/L) compared with gemfibrozil given alone (62.6 +/- 10.3 mg*hr/L) which was statistically different by both ANOVA and paired t-test. This finding suggests a decrease in gemfibrozil bioavailability. Cmax when colestipol was given with gemfibrozil (14.7 +/- 6.6 mg/L) was not statistically different from gemfibrozil alone (20.1 +/- 4.9 mg/L). However, the mean serum concentrations when gemfibrozil was given with colestipol were significantly lower at the 0.5, 1.0 and 1.5 hour sampling times when compared to the other regimens. Gemfibrozil serum elimination half-life was not significantly altered by combination with colestipol. The data suggest a reduction of gemfibrozil bioavailability when colestipol is administered concomitantly. Separating the administration of these two drugs by at least two hours will avoid this drug interaction.

The pharmacokinetics of the oral cephalosporins--a review

The pharmacokinetics of the older and more recent oral cephalosporins are reviewed. With the exception of cefadroxil the older agents (cephalexin, cephradine and cefaclor) have serum elimination half-lives of less than or equal to 1 h and hence have to be administered three to four times daily. The urinary recovery of these agents is high (greater than 80% of oral dose) with the exception of cefaclor (54%). Cefaclor is also chemically unstable. The newer agents can be divided into those that are prodrugs (cefpodoxime proxetil and cefuroxime axetil) and compounds that are absorbed as such (cefixime, cefprozil and ceftibuten). They all have half-lives greater than 1.25 h and can be given once or twice daily. The penetration of these agents into an inflammatory exudate was studied and found to be cefixime 132%, ceftibuten 113%, cefpodoxime 104%, cefuroxime 92% and cefprozil 79% of the serum concentration. The penetration of cefpodoxime and cefixime into the respiratory tract was also studied; the mean percentage bronchial mucosal penetration was 52% for the former and 38% for cefixime. The urinary recovery of these newer agents (with the exception of ceftibuten) tends to be less than that of the earlier agents. There was a relationship between the serum elimination half-life of these agents and the degree of tissue penetration, those agents with longer half-lives penetrating to a greater extent.

Penetration of cefoperazone into ascites

The pharmacokinetics of cefoperazone was studied in eleven cirrhotic patients with ascites after i.v. administration of a single dose of 15 mg.kg-1 (n = 7) or after three doses of 15 mg.kg-1 given at 12 h intervals (n = 4). The concentrations of cefoperazone in serum and ascitic fluid were determined by HPLC. The peak serum cefoperazone concentration after a single i.v. injection of 15 mg.kg-1 was 96.0 mg.l-1. The serum elimination half-life was longer (5.0 h) than in normal subjects. The penetration of cefoperazone into ascites was satisfactory (32.3% and 58.3% after single and repeated injections, respectively). Ascitic fluid concentrations of cefoperazone exceeded 5.4 mg.ml-1 from 0.5 to 6 h after the single i.v. injection, levels which are well above the MIC of most pathogens found in spontaneous bacterial peritonitis. Adjustment of the dose of cefoperazone in cases of severe hepatic insufficiency does not appear to be necessary provided that renal function is normal.

Cetirizine: A pharmacokinetic and pharmacodynamic evaluation in children with seasonal allergic rhinitis

In a double-blind, randomized, parallel-group 5-week study, cetirizine, 5 mg or 10 mg daily, was ingested by 10 and nine children, respectively. Cetirizine was rapidly absorbed with mean peak cetirizine concentrations of 427.6 ± SD, 144.2 ng/ml. 1.4 ± 1.1 hours after the 5 mg dose, and 978.4 ± 340.6 ng/ml, 0.8 ± 0.4 hours after the 10 mg dose. The dose-independent serum-elimination half-life of cetirizine was 7.1 ± 1.6 hours after cetirizine, 5 mg, and 69 ± 1.6 hours after cetirizine, 10 mg. Urinary excretion of unchanged cetirizine during 24 hours after the initial dose of cetirizine, 5 mg, was 40 ± 15%, and after cetirizine, 10 mg, it was 39 ± 14%. The mean histamine-induced wheal-and-flare areas were significantly suppressed from 1 to 24 hours after the first dose of cetirizine, 5 mg, and from 1 2 to 24 hours after the first dose of cetirizine, 10 mg, compared to the mean predose wheal-and-flare areas ( p < 0.01). During daily dosing with cetirizine, 5 mg or 10 mg at bedtime for 35 days, serum cetirizine concentrations and suppression of histamine-induced wheals and flares were monitored every 7 days, 12 hours after the cetirizine dose. The mean serum cetirizine concentrations remained relatively stable during this time, and the mean wheal-and-flare areas remained significantly suppressed ( p < 0.01) compared to baseline wheal-and-flare areas measured before the first dose of cetirizine. The symptoms and signs of allergic rhinitis were suppressed throughout the study by cetirizine, 5 mg and 10 mg. No sedation, dry mouth, or other adverse effects were reported at any time. Cetirizine is a potent, new H 1-receptor antagonist without central nervous system or anticholinergic activity. No evidence of subsensitivity to cetirizine was found during 5 weeks of treatment.

Clinical pharmacokinetics of cefotiam.

Cefotiam, a semisynthetic parenteral cephalosporin of the aminothiazole group, exhibits interesting properties: stability against hepatic metabolism and excellent solubility, accounting for an apparent volume of distribution 2 to 3 times higher than that of most other cephalosporins. Its degree of protein binding is about 40%. High concentrations of cefotiam are observed in several tissues (kidney, heart, ear, prostate and genital tract) as well as in fluids and secretions (bile, ascitic fluid). In healthy subjects, the serum elimination half-life is about 1 hour. The pharmacokinetics are linear only for doses lower than 1g. Cefotiam is mostly (and rapidly) eliminated in unchanged form in urine; 50 to 70% of the dose is recovered during the 12 hours following administration, and only severe renal failure, with creatinine clearance less than 5 ml/min, significantly alters the elimination half-life. Although the drug has no proven nephrotoxicity in man, a reduction of the dose is recommended when creatinine clearance is less than 30 ml/min.

The Pharmacokinetics and Pharmacodynamics of Hydroxyzine in Patients with Primary Biliary Cirrhosis

Hydroxyzine, a potent H1-receptor antagonist often used for relief of pruritus in patients with hepatic dysfunction, was studied in eight patients, mean age 53.4 +/- SD 11.2 years, with primary biliary cirrhosis. The patients ingested a single dose of hydroxyzine, 0.7 mg/kg (mean dose 43.9 +/- 6.6 mg). Before the dose, then hourly for 6 hours, every 2 hours from 6-12 hours, at 24 hours, and every 24 hours for 6 days, serum hydroxyzine and cetirizine were measured and an intradermal injection of 0.01 mL of a 0.1 mg/mL solution of histamine phosphate was performed. Wheals and flares were traced at 10 minutes and the areas were calculated. Mean peak hydroxyzine levels of 116.5 +/- 60.6 ng/mL occurred at 2.3 +/- 0.7 hours and mean peak cetirizine levels of 500.4 +/- 302.0 ng/mL occurred at 4.8 +/- 2.8 hours. The mean serum elimination half-life of hydroxyzine was 36.6 +/- 13.1 hours, and the mean serum elimination half-life of cetirizine was 25.0 +/- 8.2 hours. The mean hydroxyzine clearance rate was 8.65 +/- 7.46 mL/min/kg, and the mean volume of distribution was 22.7 +/- 13.3 L/kg. The mean wheal area was suppressed (P less than 0.01) from 1 to 120 hours, with maximal suppression from 2 to 48 hours. The mean flare area was suppressed from 1 to 144 hours, with maximal suppression from 3 to 24 hours (P less than 0.01). All patients became sleepy from 0.5 to 6 hours. Blurred vision, dizziness and dry mouth each occurred in two patients. Hydroxyzine elimination is impaired in patients with primary biliary cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefmetazole (CS-1170), a "new" cephamycin with a decade of clinical experience.

In vitro and in vivo study results were reviewed from cefmetazole, a "new" parenteral cephamycin. Cefmetazole's spectrum of activity was comparable to that of second-generation cephalosporins, which includes clinical coverage of many Enterobacteriaceae, Staphylococcus spp., streptococci, Haemophilus spp., pathogenic Neisseria, Branhamella catarrhalis, and anaerobic bacteria. Cefmetazole was generally more potent (two- to eightfold) than cefoxitin against organisms within their spectrums and was particularly active for staphylococci (MIC90, 2.0 micrograms/ml). Methicillin-resistant S. aureus strains were more susceptible to cefmetazole alone or in combination (fosfomycin) than any other cephamycin. Cefmetazole has demonstrated excellent stability to aerobic and anaerobic organism-produced beta-lactamases. It also inhibits Type I cephalosporinases and, uniquely, some other cephalosporinases produced by the Bacteroides. This superior stability, enzyme interaction, and better penetration into bacterial cells results in a sustained bactericidal effect and a capacity for more infrequent dosing. The cefmetazole serum elimination half-life was 1.5 hr, also justifying use at greater than or equal to 8-hr intervals. Clinical trials in the United States and Japan demonstrated an acceptably high cefmetazole infection cure rate (88% to 100%), especially in direct comparative studies with cefoxitin. Cefmetazole was also proven very effective in minimizing infectious wound morbidity (prophylaxis) using 2 g single- or multidose regimens. Adverse drug reactions were usually minor; in the Japanese surveillance trial (118,318 patients) the rate was only 2.2% (8.8% in United States). Cefmetazole has been extensively and safely used in Japan since 1980.

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 lomefloxacin's elimination.

A comparative study of the pharmacokinetics of propranolol and its major metabolites in the rat after oral and vaginal administration

1. The concentrations of propranolol (PPL) and its metabolites were monitored by h.p.l.c. in serum of rats during the first 6 h after administering single doses (20 mg/kg) of PPL either orally or intravaginally (i.vg). 2. The results showed that PPL was quickly transferred to the systemic circulation from the rat vagina and the serum concentration profile as substantially altered by the route of administration. Serum concentrations of free PPL were significantly higher in i.vg-dosed animals than their oral dosed counterparts. 3. Inter-animal serum conc. variations of PPL and its metabolites in the i.vg-dosed rats were smaller than those of the orally treated females. 4. In comparison with the i.vg-dosed rats, the levels of PPL metabolites (propranolol glycol, naphthoxylactic acid, naphthoxyacetic acid) were greater by the oral route, though these differences were not statistically significant. 5. The serum elimination half-lives (t1/2)beta of PPL and its metabolites during the beta-phase were not significantly different in the two treatment groups. 6. Following i.vg application, both the AUC and the Cmax values of PPL were significantly greater than those of orally dosed females, while no statistically significant differences were found in the tmax values. 7. Comparison of the AUC values showed that relative bioavailability of PPL was approx. 36 times greater in i.vg-treated animals than those of the orally dosed rats.

Cefixime, in-vitro activity, pharmacokinetics and tissue penetration.

The in-vitro activity of cefixime was studied with clinical isolates and compared with that of other agents. Cefixime exhibited good activity against the Enterobacteriaceae, Haemophilus influenzae, and Neisseria gonorrhoeae, including beta-lactamase producing strains. Activity was also high against Streptococcus pneumoniae and group A and group B beta-haemolytic streptococci. Staphylococcus aureus, faecal streptococci, anaerobic bacteria and Pseudomonas aeruginosa were not susceptible. Activity against susceptible isolates was comparable to cefotaxime and was normally superior to cefuroxime, cephalexin and amoxycillin. The pharmacokinetics of cefixime were studied in six healthy male volunteers, each receiving a 400 mg oral dose following an overnight fast. Tissue penetration of the antibiotic was estimated with a cantharides-induced blister method. The mean serum elimination half-life was 3.8 h, the mean peak concentration was 3.7 mg/l. Penetration into tissue fluid was rather slow [Tmax 6.7 h) but percentage penetration was high (132.6%). Urinary excretion was low with a 24 h recovery rate of less than 20%, though the concentrations achieved in urine exceeded the MICs of most common urinary tract pathogens for up to 24 h post-dose.

Lack of subsensitivity to terfenadine during long-term terfenadine treatment

Eleven healthy male volunteers ingested térfenadine, 60 mg, every 12 hours for 56 days. Compliance was monitored strictly throughout the study. Before the first terfenadine dose on day 0, and 12 hours after the evening terfenadine dose every seventh day and on randomly selected “unscheduled” days, wheal-and-flare areas were measured after intradermal injections of 0.01 ml of histamine phosphate (1.0 mg/ml and 0.1 mg/ml). On days 0, 28, and 56, six volunteers had skin tests hourly for 12 hours after the morning terfenadine dose. On all study days, serum terfenadine metabolite I concentrations were measured each time histamine skin tests were performed. On days 7, 14, 21, 28; 35, 42, 49, and 56, the mean areas of the histamine-induced wheals did not differ significantly from each other but were significantly decreased compared to the mean wheal area on day 0 ( p < 0.01). On these days, the mean areas of the histamine- induced flares also did not differ significantly from each other but remained significantly suppressed compared to the mean flare areas on day 0 ( p < 0.01). Wheal-and-flare suppression was noted in all unscheduled histamine skin tests performed 12 hours after the evening terfenadine dose. In the subgroup of volunteers who had hourly tests, on day 0, the mean wheal-and-flare areas were significantly suppressed from 2 to 12 hours after the dose, with maximal wheal suppression occurring at 5 hours ( p < 0.05) and maximal flare suppression occurring from 3 to 9 hours ( p < 0.01). On day 28 in the subgroup, the mean wheal area was significantly larger 12 hours after the dose than before the dose or at any other time ( p < 0.01), but the mean flare areas did not differ significantly at any time ( p = 0.01). On day 56 in the subgroup, the mean wheal areas did not differ significantly from before the dose to 12 hours after the dose, nor did the mean flare areas differ significantly at any time ( p = 0.01). The mean serum concentration of terfenadine metabolite 112 hours after the evening dose did , not differ significantly on days 7, 14,21, 28, 35, 42, 49,adn 56 ( p = 0.01). Unscheduled serum terfenadine metabolite I concentrations measured 12 hours after the dose provided additional confirmation of compliance. In the subgroup, the mean serum elimination half-life value and the mean area under the serum concentration versus time curve of terfenadine metabolite I did not differ significantly on day 0, day 28, or day 56 ( p = 0.01). We conclude that subsensitivity to the antihistaminic effect of terfenadine did not develop during 56 days in compliant subjects, as evidenced by continued suppression of the histamine-induced wheals and flares. Also, the pharmacokinetics of terfenadine metabolite 1 remained unchanged after 56 days of terfenadine treatment.

Clinical pharmacokinetics and tolerance of fleroxacin in healthy male volunteers.

The tolerance and pharmacokinetics of fleroxacin were studied in healthy male adult volunteers. The peak serum concentrations of unchanged fleroxacin were about 1.5, 3 and 5 mg/l at 1-2 h after single oral doses of 100, 200 and 400 mg, respectively. The apparent serum elimination half-life was about 10 h, independent of the dose. Fleroxacin, demethyl fleroxacin and fleroxacin N-oxide excreted in urine over 3 days accounted for about 75%, 5% and 5%, respectively, of the doses. The urine concentrations of unchanged drug were dose-related; the mean concentrations, sustained over 24 h, were about 50, 100 and 150 mg/l after 100, 200 and 400 mg doses, respectively. Food intake did not significantly influence the serum concentration and urinary excretion. Steady state serum concentrations were achieved from day 3 onwards by repeated doses of twice-a-day dosage regimen and were 2-4 and 5-9 mg/l after 200 and 400 mg bid, respectively. The mean concentrations of unchanged drug in urine were about 200 and 300 mg/l at the respective dosages. The pattern of urinary metabolites was not changed by repeated doses and 90% of repeat doses was recovered in urine, including metabolites. The serum protein binding of fleroxacin was 32%. The saliva concentration was 40% of the total serum concentration or 60% of the free serum concentration. The faecal recovery over 3 days was 3% of the dose following a single 200 mg dose after a meal. The unchanged drug concentrations in faeces during 400 mg repeated dosing were 100-150 mg/kg. No severe dose-related side-effects were observed during the study.

The pharmacokinetics of ofloxacin and a review of its tissue penetration.

The pharmacokinetics of ofloxacin were studied in six healthy volunteers following a 600 mg oral dose. The concentration of the compound was measured in serum, inflammatory fluid and urine. Ofloxacin was rapidly absorbed, the mean maximum concentration of ofloxacin being 10.7 mg/l at 1.2 h. The mean serum elimination half-life was 7 h and 80.3% of the administered compound was recovered in the urine by 48 h. Ofloxacin penetrated the inflammatory fluid well, the mean peak level being 5.2 mg/l at 5.3 h. A review of the tissue penetration is presented which indicates that the high volume of distribution of ofloxacin is associated with good tissue penetration.

Pharmacokinetics of intraperitoneal teicoplanin in patients with chronic renal failure on continuous ambulatory peritoneal dialysis.

The pharmacokinetic profile of teicoplanin, a new glycopeptide antibiotic active against Gram-positive aerobic and anaerobic bacteria, is described in five patients with end-stage renal disease on continuous ambulatory peritoneal dialysis (CAPD). A single 3 mg kg-1 dose was given intraperitoneally in the dialysate during a 6 h dwell time. The drug appeared in the plasma within 15 min at 1.00-0.28 mg l-1 (mean +/- s.d. = 0.70 +/- 0.45) in all five subjects, and peak serum concentrations ranged from 5.53 to 2.80 mg l-1 (4.84 +/- 1.43) at 6 h. Approximately 70% (71 +/- 12) of teicoplanin was absorbed from the peritoneal dialysis fluid during a single 6 h dwell time. The rate constant for peritoneal transfer (lambda d) averaged 0.318 h-1 and the half-life (t1/2 lambda d) was 2.18 h. Further values were serum elimination half-life 114-173 h; total body clearance 263-532 ml h-1; steady-state volume of distribution 68-93 l. This drug profile closely agrees with data reported after intravenous injection in patients on CAPD and suggests that teicoplanin has bidirectional exchange characteristics through the peritoneal membrane, although transfer from the systemic circulation to peritoneal fluid is consistently low. Instillation of teicoplanin in CAPD fluid may be a useful route of administration for treatment of peritonitis and exit site infections in CAPD patients.

Cefotetan: A perspective for the surgical patient

The data have shown that cefotetan has comparable clinical effectiveness when compared with cefoxitin in surgical prophylaxis and in patients with mild-to-moderate polymicrobial infection. This experience has consistently focused on the longer serum elimination half-life of cefotetan, which allows the antibiotic to be given less often than shorter half-life alternatives. A more extensive experience in seriously ill patients is necessary to further address 1) the use of cefotetan as an alternative to combination antibiotic therapy; 2) the risks of the anaerobic DOT group or enterococcal failure; and 3) potential clinical expression of any bleeding diathesis. The initial clinical experience reported herein appears favorable.

Pharmacokinetics of enprofylline administered intravenously and as a sustained-release tablet at steady state in children with asthma

The pharmacokinetics of enprofylline (3-propylxanthine) were studied in 10 children with asthma (mean age 7.9 years), after enprofylline 1 mg/kg given intravenously and after enprofylline 7.5 +/- 1.3 mg/kg given as a sustained-release tablet after 8 days of oral dosing twice daily. The mean +/- SD enprofylline serum elimination half-life was 1.06 +/- 0.20 hours, considerably shorter than the half-life reported in adults. The mean steady-state volume of distribution was 0.55 +/- 0.05 L/kg. The mean clearance rate was 0.44 +/- 0.06 L/hr/kg. The mean enprofylline serum concentration at steady state was 1.7 +/- 0.5 mg/L. The mean peak to trough ratio was 3.02 +/- 1.31. On the first and ninth study days, 87% +/- 8% and 90% +/- 16%, respectively, of the dose of enprofylline was recovered as unchanged drug in the urine. Enprofylline has a short half-life in children, but the sustained-release formulation provides stable serum concentrations and satisfactory relief of asthma throughout the 12-hour dosing interval.

Drug interactions in surgical patients

The treatment of drug overdose with drug-specific antibody fragments may require very high antibody doses. To address the feasibility of this therapy, we studied the pharmacokinetics and toxicity of high-dose human nonspecific Fab fragments in beagles. Three dogs received 5.3 g/kg Fab iv over 1 hr. Because nephrotoxicity was observed, three subsequent dogs received 3.2 g/kg. The fraction of the Fab dose excreted in urine (10 ± 6%) was lower than reported values for either high or low doses of Fab in other species. The terminal serum elimination half-life (42 hr for the higher and 48 hr for the lower dose) was also longer than reported values for other species, due to lower renal and nonrenal Fab clearance. Fab administration was tolerated without adverse hemodynamic effects. One of three dogs at each dose developed transient oliguria. All dogs developed a transient but marked increase in the serum creatinine concentration. At 2 weeks creatinine clearance had returned to normal. Urinary protein and albumin excretion at 2 weeks were within the normal range for dogs but were increased over their baseline values. The histology of all organs was normal at 3 weeks by light microscopy, and renal histology by electron microscopy was also normal. The mechanism of Fab nephrotoxicity, not observed previously with high-dose Fab in rats or lower doses of Fab in other species including dogs, is not clear. These data suggest that further study of the potential toxicity of high-dose Fab, and its reversibility, is needed to assess the feasibility of treating drug overdose with this antibody fragment. The long terminal half-life of high-dose Fab in the dog and its low renal clearance contrast with values observed with lower doses of Fab in other species but would not be expected to preclude the use of high-dose Fab for drug overdose.

Clinical pharmacokinetics of midazolam in intensive care patients, a wide interpatient variability?

The pharmacokinetics of midazolam and its metabolites were studied in 17 patients on mechanical ventilation in a general intensive care unit who were receiving a continuous intravenous infusion of midazolam, adjusted according to the level of induced sedation. Three patients were studied twice. Serum midazolam and alpha-hydroxymidazolamglucuronide levels were determined during and after infusion. The sedation level was scored on a four-point scale. Half of the observed patients were still drowsy or asleep 10 hours after termination of midazolam infusion. In only one patient was midazolam serum elimination half-life less than 2 hours and in six patients the half-life was greater than 10 hours. A wide range of midazolam serum levels was associated with adequate sedation, and similarly the midazolam levels at the moment of awakening were highly variable. The serum concentration ratio of midazolam/alpha-hydroxymidazolamglucuronide at the end of the infusion varied from 0.03 to 15.6. Renal function could account for only a part of this variation.

Pharmacokinetics of the Quinolones in Volunteers: A Proposed Dosing Schedule

The pharmacokinetics and tissue penetration of five quinolones into inflammatory exudate were studied in healthy volunteers. The compounds studied were norfloxacin (400 mg orally), enoxacin (400 mg intravenously and 600 mg orally), ciprofloxacin (100 mg intravenously and 500 mg orally), ofloxacin (600 mg orally), and pefloxacin (400 mg intravenous). Orally administered ofloxacin and ciprofloxacin were the most rapidly absorbed (time to maximal serum level, 1.2 hours) and enoxacin the least (1.9 hours). The serum levels attained were highest in the case of ofloxacin (after an allowance was made for the higher dose administered). The serum elimination half-lives were as follows: norfloxacin, 3.75 hours; ciprofloxacin, 3.9 hours (oral) and 4.0 hours (intravenous); ofloxacin, 7.0 hours; enoxacin, 6.2 hours (oral) and 5.1 hours (intravenous); and pefloxacin, 10.5 hours. All agents penetrated well into a mild inflammatory exudate. The 24-hour recovery rate from urine was 62% for oral enoxacin, 46.4% for intravenous enoxacin (plus 12.2% for oxo-enoxacin), 27% for norfloxacin, 30.6% for oral ciprofloxacin, 75.7% for intravenous ciprofloxacin, 73% for ofloxacin, and 4.9% for pefloxacin (plus 9.2% for the norfloxacin metabolite and 17.8% for pefloxacin N-oxide). A dosing schedule for the quinolones was proposed on the basis of pharmacokinetic parameters and microbiologic activity.

Pharmacokinetics and tissue penetration of cefpirome, a new cephalosporin.

The pharmacokinetics and tissue penetration (as measured by a blister fluid model) of cefpirome were studied in six male volunteers following a 1 g intravenous dose. A mean peak serum concentration (at 5 min) of 97.4 mg/l was followed by rapid distribution into an apparent volume of 21.3 1. The serum elimination half-life was 2.3 h. Cefpirome penetrated rapidly into inflammatory fluid with a mean peak concentration of 39.2 mg/l at 1.9 h. The mean inflammatory fluid elimination half-life was 2.5 h. The availability of the drug in inflammatory fluid was high with a mean per cent penetration of 123%. The plasma and renal clearances were 109.5 and 82.1 ml/min respectively. Twenty-four hour urinary recovery was 75.5% of the administered dose. This study suggests that a twice daily dosage may be sufficient to treat tissue infections with susceptible pathogens.