Homologous radioimmunoassay of human osteocalcin.

Osteocalcin or bone gamma-glutamic acid-containing protein (GLA protein) was isolated from human bone and used to develop a homologous radioimmunoassay of human osteocalcin. The effect of age on serum osteocalcin was studied in 380 normal children and adolescents and 330 normal adults. The mean (+/- SD) values in adults were higher in men [25 +/- 5 micrograms/L (4.3 +/- 0.8 nmol/L)] than in premenopausal women [20 +/- 6 micrograms/L (3.4 +/- 1.0 nmol/L); P < 0.01], but both were lower than in postmenopausal women [29 +/- 2 micrograms/L (5.0 nmol/L)]. The highest concentrations were seen in girls [ages 10-12 years: 99 +/- 38 micrograms/L (17.0 nmol/L)] and boys [ages 14-16 years: 107 +/- 57 micrograms/L (18.4 nmol/L)]. These mean values were substantially higher than those previously reported for results of heterologous osteocalcin radioimmunoassays but the correlation (r = 0.87, n = 77, P < 0.001) between both sets of results was excellent. In patients with metabolic bone diseases characterized by high or low bone turnover, the increase or decrease in serum osteocalcin observed was as expected. This homologous radioimmunoassay of human osteocalcin thus reflects bone turnover but reports serum concentrations higher than previously suspected.     

Osteocalcin concentrations in plasma prepared with different anticoagulants

We investigated the effects on plasma osteocalcin concentrations of different anticoagulants used to collect the blood samples. Plasma osteocalcin concentrations measured by enzyme immunoassay and radioimmunoassay are influenced by the nature of the anticoagulants used. The most significant difference between concentrations found in plasma and serum was seen with oxalate/fluoride anticoagulant, which reduced osteocalcin concentrations to 37.3% of serum values. This is probably related to increased hemolysis with this anticoagulant compared with osteocalcin concentrations in plasma prepared with other anticoagulants. Samples prepared with sodium citrate (0.105 mol/L) or lithium heparin gave values 92.4% and 83.6% of those obtained with matched serum samples. Osteocalcin concentrations were relatively stable in plasma and serum at -20 degrees C for two freeze/thaw cycles. In blood from 100 patients there was a good correlation between osteocalcin concentrations in serum and plasma (lithium heparin) (r2 = 0.831); the slope and intercept (+/- SE) were 0.924 +/- 0.04 and 4.92 +/- 1.25 micrograms/L, respectively. However, in 10 patients, serum osteocalcin concentrations were two- to threefold higher than those in matched plasma samples.     

Hemodynamic and metabolic effects of epinephrine during cardiopulmonary resuscitation in a pig model.

BACKGROUND AND METHODS: This study was designed to assess the effect of epinephrine during cardiopulmonary resuscitation (CPR) on left ventricular myocardial blood flow, systemic oxygen delivery and consumption, and on plasma glucose and lactate concentrations. Fourteen pigs were allocated to receive either 0.9% saline (n = 7), or 45 micrograms/kg epinephrine (n = 7) after 5 mins of ventricular fibrillation, and 3 mins of open-chest CPR. Left ventricular myocardial blood flow was measured with radiolabeled microspheres. Plasma catecholamine concentrations were measured by high-pressure liquid chromatography. RESULTS: During open-chest CPR, mean (+/- SD) values of left ventricular myocardial blood flow before, 90 secs, and 5 mins following drug administration were 49 +/- 10, 46 +/- 12, 43 +/- 15 mL/min/100 g, respectively, in the control group, and 52 +/- 12, 118 +/- 21, 84 +/- 28 mL/min/100 g, respectively, in the epinephrine group (p less than .05 at 90 secs and 5 mins). At the same time points, mean (+/- SD) oxygen delivery indices were 7.7 +/- 3.0, 6.0 +/- 2.1, 6.5 +/- 2.7 mL/min/kg in the control group and 7.6 +/- 2.5, 5.3 +/- 2.1, 5.5 +/- 1.9 mL/min/kg in the epinephrine group (nonsignificant). Mean oxygen consumption indices were 5.8 +/- 2.4, 4.6 +/- 1.6, 5.2 +/- 2.6 mL/min/kg in the control group and 5.4 +/- 1.6, 4.2 +/- 1.6, 4.4 +/- 1.4 mL/min/kg in the epinephrine group (nonsignificant). During CPR and before epinephrine administration, arterial plasma epinephrine concentrations increased from prearrest values of 0.77 +/- 0.70 to 62.1 +/- 48.7 micrograms/L, and plasma norepinephrine concentrations increased from 0.28 +/- 0.32 to 104.3 +/- 57.1 micrograms/L. After administered epinephrine, there was an additional increase to 271 +/- 83 micrograms/L at 90 secs in arterial plasma epinephrine, but no important alteration in the plasma norepinephrine concentration. At no time point could we find a clinically important difference in plasma glucose or lactate concentrations between the two groups. CONCLUSIONS: At a dose of 45 micrograms/kg, epinephrine caused an increase in left ventricular myocardial blood flow after a total of 8 mins of cardiac arrest, including 3 mins of CPR, while not altering systemic oxygen delivery and consumption, plasma glucose, or lactate concentrations.     

The effect of estrogen replacement therapy on total plasma homocysteine in healthy postmenopausal women

OBJECTIVE: To clarify the effect of estrogen on total plasma homocysteine concentration and on the concentration of vitamins required for homocysteine metabolism (folate, vitamin B12, and vitamin B6). METHODS AND RESULTS: We measured total fasting plasma homocysteine in 16 healthy postmenopausal women before and 6 hours after a methionine load (100 mg/kg); fasting concentrations of folate, vitamin B12, vitamin B6, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were also determined. After 6 months of estrogen replacement therapy with estradiol, 2 mg daily, and 1 cycle of quarterly methoxyprogesterone acetate, 5 mg daily administered on the 91st through 100th days, measurements were repeated. There was no significant change in mean +/- SD fasting homocysteine concentration (8.8+/-2.5 vs 8.5+/-2.0 micromol/L; P=.30); homocysteine concentrations after methionine load increased from 38.8+/-12.3 to 51.1+/-12.5 micromol/L (P=.01). During this time period, no significant changes occurred in the concentrations of folate (11.7+/-4.4 vs 9.8+/-4.1 nmol/L; P=.06), vitamin B12 (394+/-182 vs 411+/-155 pmol/L; P=.40), or vitamin B6 (pyridoxal phosphate) (26+/-21 vs 36+/-25 nmol/L; P=.15). The mean +/- SD concentration of low-density cholesterol declined 20% (from 147+/-32 to 118+/-37 mg/dL) and high-density lipoprotein increased 16% (from 40+/-13 to 46+/-19 mg/dL) during the study period. CONCLUSIONS: Six months of estrogen replacement therapy did not lower fasting plasma total homocysteine concentrations and raised homocysteine concentrations following a methionine load. Lipid profiles improved significantly during the study period. A reduction in homocysteine concentrations is not likely to contribute to the reduction in cardiovascular events seen with estrogen replacement therapy.     

Liquid chromatography and fluorescence polarization immunoassay methods compared for measuring flecainide acetate in serum

We analyzed 99 patients' serum samples for concentrations of a new antiarrhythmic agent, flecainide acetate, by fluorescence polarization immunoassay (FPIA) and "high-performance" liquid chromatography (HPLC). Within-day and between-day coefficients of variation at concentrations in the low and high ends of the therapeutic range were less than 7% for HPLC and less than 9% for FPIA. There was no statistical difference in the mean (+/- SD) concentrations of the clinical serum samples measured by the two methods (607 +/- 334 micrograms/L by HPLC, 602 +/- 344 micrograms/L by FPIA), but results by each differed by a mean of 0.13%. FPIA and HPLC measurements correlated significantly (r = 0.98, P less than 0.05), and were linearly related (slope = 0.970, intercept = 13 micrograms/L) as assessed by orthogonal regression. Both assay methods produced similar concentration measurements and were sufficiently accurate and precise to be used in therapeutic drug monitoring.     

Dialyzable free cortisol after stimulation with Synacthen

OBJECTIVES: To compare the changes in free vs. total serum cortisol concentrations after acute stimulation of the adrenal cortex. DESIGN AND METHODS: Paired serum samples of ten individuals taken immediately before and 1 h after stimulation with 250 microg ACTH (1-24) (Synacthen) given i.v. were analyzed. Total cortisol was quantified using liquid chromatography tandem-mass spectrometry with an online sample extraction system and tri-deuterated cortisol as the internal standard. Free cortisol was measured with the same method after equilibrium dialysis. Concentrations of the corticosteroid-binding globulin (CBG) were determined by radioimmuno assay. RESULTS: Total cortisol increased by a mean of 106% (mean basal cortisol 312 nmol/L (SD 140 nmol/L), stimulated 686 nmol/L (SD 163 nmol/L); p < 0.001, paired t-test for differences); no significant change of CBG concentrations was found (874 nmol/L (SD 179 nmol/L) before stimulation, 869 nmol/L (SD 225 nmol/L) after stimulation). The mean increase of free cortisol was 263% (mean basal free cortisol 20.3 nmol/L (SD 13.2 nmol/L), stimulated 73.8 nmol/L (SD 26.7 nmol/L); p < 0.001) and thus substantially more pronounced compared to the increase of total cortisol (p < 0.01). The ratio of free to total serum cortisol was significantly increased after stimulation (6.1% (SD 1.7%) before stimulation, 10.6% (SD 1.9%) after stimulation; p < 0.001). CONCLUSIONS: After acute neuroendocrine stimulation of the adrenal cortex the relative increase of free bioactive cortisol concentrations is substantially more pronounced than the increase of total cortisol concentrations.     

Solid-phase enzymoimmunoassay for osteocalcin in human serum or plasma, with use of a monoclonal antibody

In this solid-phase enzymoimmunoassay on microtiter plates for osteocalcin in serum or plasma, we use an osteocalcin-horseradish-peroxidase conjugate and a monoclonal antibody raised against bovine osteocalcin. We thoroughly standardized the assay for measurement of osteocalcin in both serum and plasma, demonstrating independence of sample volume, and determining the analytical recovery and within-and between-assay CVs. The detection limit was between 0.6 and 1.1 micrograms/L and the ED50 was 16 micrograms/L for a 5-microL sample volume. The intra-assay CV over the range 3 to 74 micrograms/L was less than or equal to 15%. The interassay CV over the range 3.6 to 46 micrograms/L was less than or equal to 16%. Results by this assay and by an in-house radioimmunoassay in which the same monoclonal antibody was used correlated well (r2 = 0.948). Osteocalcin concentrations in serum and plasma as measured with the present assay agreed well with published values.     

Digoxin-verapamil interaction: reduction of biliary but not renal digoxin clearance in humans

The interaction between digoxin and verapamil was studied in six patients (mean age +/- SD, 61 +/- 5 years) with chronic atrial fibrillation. The effects of adding verapamil (240 mg/day) on steady-state plasma concentrations and renal and biliary clearances of digoxin were studied in a crossover manner. The biliary clearance of digoxin was determined by a duodenal perfusion technique. Verapamil induced a 44% increase in steady-state plasma concentrations of digoxin, from 0.80 +/- 0.24 to 1.15 +/- 0.40 nmol/L (p less than 0.01). The biliary clearance of digoxin decreased by 43%, from 187 +/- 89 to 101 +/- 55 ml/min (p less than 0.05), in the presence of verapamil, whereas the renal clearance was unaffected (153 +/- 31 versus 173 +/- 51 ml/min; difference not significant). Our results indicate that the main inhibitory effect of verapamil on digoxin elimination is on the biliary route.     

Growth hormone and cortisol secretion in patients with burn injury.

A prospective study of growth hormone, insulin-like growth factor (IGF-1), and cortisol secretion was undertaken in six adults with burn injury. Serum concentrations of growth hormone and IGF-1 were low in all patients during the first 2 weeks of hospitalization. The mean growth hormone level was 4.35 +/- 0.83 micrograms/L on day 1 and 1.70 +/- 0.50 micrograms/L on day 13. The mean serum concentration of IGF-1, which reflects overall growth hormone secretion, was 0.43 +/- 0.09 U/ml on day 1 and 0.61 +/- 0.11 U/ml on day 13; these values are distinctly low. After 3 to 4 weeks, IGF-1 concentrations increased to the mid-normal range, whereas growth hormone values did not change. Morning plasma cortisol concentrations were modestly elevated; however, urine free cortisol concentrations, which reflect total cortisol secretion, were elevated 2 to 28 times above normal values at the time of admission (mean, 443.5 +/- 323.7 nmol/L). Urinary free cortisol concentrations remained elevated after 2 weeks (mean, 230.5 +/- 94.5 nmol/L). Patients with burn injury have inappropriately low growth hormone secretion and IGF-1 production in spite of the stress of the injury and more than adequate nutritional therapy.     

Improved determination of vanadium in biological fluids by electrothermal atomic absorption spectrometry

We made sensitive and accurate electrothermal atomic absorption spectrometric measurements of vanadium in small volumes of serum. The wet-digested sample was extracted into an organic solvent, with N-benzoyl-N-(o-tolyl)hydroxylamine (BTA) as the chelating reagent. After evaporating the solvent, we dissolved the residue in acetic acid, and injected a 60-microL aliquot into a graphite furnace. In this way we could measure vanadium concentrations as low as 80 ng/L in 4 mL of serum. The within-run CV was 3.3% for serum, 7.7% for urine. Analytical recoveries of vanadium added to serum and urine were 90.3% and 90.8%, respectively. We measured vanadium concentrations in sera from 64 healthy persons (group 1), 15 nondialyzed uremic patients (group 2), and 11 hemodialyzed patients (group 3). The highest concentration of vanadium in group 1 was 240 ng/L; about 60% of the values for this group were less than 80 ng/L. In group 3, the vanadium concentrations were extremely high (15 +/- 14.2 micrograms/L, mean +/- SD), less so (but still above normal) in group 2 (1.58 +/- 3.16 micrograms/L).     

Atomic absorption spectrometric determination of selenium in human blood components

We separated blood from five healthy blood donors into plasma, erythrocytes, platelets, and leukocytes; counted the number of cells in each fraction; and determined the selenium content of each component by hydride generation atomic absorption spectrometry. The mean (+/- SD) selenium concentrations and amounts measured were as follows: whole blood 102.3 +/- 16.1 micrograms/L, plasma 76.9 +/- 10.6 micrograms/L, erythrocytes 13.7 +/- 2.8 ag per cell, platelets 4.8 +/- 1.1 ag per cell, and leukocytes 99 +/- 26 ag per cell.     

Time-resolved immunofluorometric assay of sex-hormone binding globulin

A time-resolved immunofluorometric assay (trlFMA) for human sex-hormone binding globulin (SHBG) is described in which antibody-coated tubes or microliter strip-wells and a europium (Eu) chelate-labeled monoclonal antibody are used. The trlFMA sensitivity is similar to that of other SHBG immunoassays, and other analytical variables compare favorably with an SHBG immunoradiometric assay (IRMA) kit and a steroid binding capacity assay: the interassay coefficient of variation (CV) is less than 8% and the intra-assay CV is less than 6% for concentrations between 6 and 200 nmol/L. The reference intervals (means +/- SD) for SHBG concentrations (nmol/L) in serum from 10 men, 10 women, and 10 pregnant women were 23 +/- 12, 65 +/- 39, and 439 +/- 122, respectively. In 14 hirsute women the mean +/- SD serum SHBG concentration (37 +/- 21 nmol/L) was significantly lower (P less than 0.01) than the mean for an age-matched, nonhirsute female comparison group. The trlFMA is technically simple, requires no centrifugation or separation reagent, and takes a counting time of only 1 s. In addition, the Eu-label is nontoxic, presents no waste-disposal problems, and has a long shelf life.     

Hyaluronan: relationship to hemodynamics and survival in porcine injury and sepsis.

BACKGROUND AND METHODS: Hyaluronan is a polysaccharide normally present in low concentrations in the blood, and is rapidly cleared from the blood by the liver. Increased plasma hyaluronan concentrations have been found in patients with sepsis. We studied changes in serum hyaluronan concentrations and their relationship to hemodynamics and survival in a 48-hr porcine model of injury and sepsis. RESULTS: Circulating hyaluronan concentrations increased to high values after induction of experimental sepsis (from mean baseline values of 242 +/- 26 [SEM] to mean maximum concentrations of 964 +/- 255 micrograms/L [p less than .01]) compared with controls (199 +/- 38 to 303 +/- 32 micrograms/L). A weak negative correlation between mean arterial pressure (MAP) and serum hyaluronan values was found (r2 = .47; p less than .01). Nonsurvivors had higher mean serum hyaluronan concentrations than survivors (603 +/- 147 vs. 285 +/- 43 micrograms/L [p less than .05]). CONCLUSIONS: Experimental sepsis is associated with an increase in serum hyaluronan values. The relationship between decreased MAP and increased serum hyaluronan concentrations could point to reduced liver perfusion as a cause. An association between high hyaluronan values and nonsurvival in sepsis is possible.     

Immunofluorometric demonstration and quantification of placental protein 5 in the absence of pregnancy

This time-resolved immunofluorometric assay (IFMA) developed for measurement of placental protein 5 (PP5) involves two antibodies: a monoclonal anti-PP5 antibody attached to a solid phase and an europium(III) chelate-labeled polyclonal anti-PP5 antibody as a tracer. The measuring range is 0.05-100 micrograms/L and the detection limit is 20 times lower than that of a PP5 radioimmunoassay (RIA) performed with the same polyclonal antiserum. By IFMA, PP5 could be detected and quantified in all plasma and serum samples of nonpregnant and pregnant individuals, whereas PP5 was undetectable by RIA in serum of healthy men and nonpregnant women. The mean concentration of PP5 in sera from men was 0.43 micrograms/L (SD 0.13, range 0.19-0.75, n = 47) and in sera from nonpregnant women 0.49 micrograms/L (SD 0.19, range 0.20-0.90, n = 41). PP5 concentrations in serum showed no systematic variation during the menstrual cycle. In serum samples from 60 pregnant women the results obtained by IFMA and RIA correlated well (r = 0.97).     

Concentrations of total and free dehydroepiandrosterone in plasma and dehydroepiandrosterone in saliva of normal and hirsute women under basal conditions and during administration of dexamethasone/synthetic corticotropin

Using a specific and sensitive radioimmunoassay involving extraction with diethyl ether and chromatographic separation of steroids, we measured concentrations of salivary and plasma dehydroepiandrosterone (DHEA) in 22 women with normal ovulatory cycles (ages 18-45 years). Salivary DHEA values closely correlated with total and free DHEA in plasma. In the follicular phase the mean concentrations of salivary and plasma free DHEA were virtually equal [mean (SD): 0.61 (0.32) and 0.56 (0.34) nmol/L, respectively]. In the luteal phase, salivary DHEA slightly exceeded the plasma free DHEA [0.68 (0.40) vs 0.56 (0.38) nmol/L, P less than 0.01]. Also, during combined dexamethasone/synthetic corticotropin administration in 25 patients with androgenizing disorders and in 10 normal subjects (each in the follicular and luteal phases), the concentration of DHEA in saliva strongly correlated with total and free DHEA in plasma. During these dynamic tests, the mean concentrations of free DHEA in plasma and salivary DHEA in the hirsute women were significantly higher than the mean concentrations in the control women at all times before and after corticotropin infusion (P less than 0.05- less than 0.0001). In contrast, plasma total DHEA in patients exceeded nonhirsute values only at 15 min after corticotropin administration. In six of 25 patients total DHEA during combined administration of dexamethasone/synthetic corticotropin exceeded normal values by at least 2 SD. The response of salivary and free DHEA to synthetic corticotropin in this subgroup was also excessive.     

Association between homocysteine and neopterin in healthy subjects measured by a simple HPLC-fluorometric method.

OBJECTIVES: Neopterin and homocysteine promote vascular smooth muscle cell proliferation through the activation of nuclear factor(kappa) B. The aim of this study was to investigate the relation between these two compounds in healthy subjects by a rapid HPLC-fluorometric method which simplifies sample pretreatment for the measurement of neopterin in serum. DESIGN AND METHODS: In 40 healthy subjects (45.9 +/- 2.1 yr, mean +/- SEM, 10 males, 30 females) serum neopterin concentrations were measured by HPLC-fluorometry and enzyme-linked immunusorbant assay-ELISA and the results were compared. Urinary neopterin and plasma total homocysteine concentrations were assayed by HPLC-fluorometry. RESULTS: Serum neopterin concentrations measured by HPLC and ELISA were 7.5 +/- 0.4 and 7.4 +/- 0.3 nmol/L, respectively, r = 0.92, p < 0.01. Urinary neopterin level was 163.9 +/- 11.0 nmol/mmol creatinine and plasma total homocysteine 7.6 +/- 0.4 micromol/L. A significant positive correlation was observed between serum neopterin and plasma total homocysteine (r = 0.59, p < 0.01). CONCLUSIONS: A simple and rapid sample pretreatment for the measurement of neopterin in serum has been introduced. The significant positive correlation between neopterin and homocysteine implies that, interference with leukocyte function might be a new possible mechanism for the deleterious effects of homocysteine on vascular function.     

Gradient centrifugation to isolate platelets for determination of trace elements by neutron-activation analysis

A nonionic iodinated compound, Nycodenz, was used for density-gradient isolation of platelets before analysis for trace elements by instrumental neutron activation. The platelet samples were almost free from plasma and erythrocytes, and the trace element contribution from additives was insignificant for the elements investigated. The reproducibility of the trace element analysis in platelets attests to the usefulness of density-gradient separation. Platelet samples were obtained twice, three weeks apart, from 10 healthy young women (ages 24 +/- 2 years). The mean (SD) concentrations were as follows: Se, 0.62 (0.16) mg/L and 4.7 (1.4) ng/10(9) platelets; Zn, 44 (10) mg/L and 333 (80) ng/10(9) platelets; Rb, 3.0 (0.5) mg/L and 23 (5) ng/10(9) platelets; and Cs, 24 (5) micrograms/L and 0.18 (0.04) ng/10(9) platelets.     

Hypokalemia in acute theophylline poisoning

The frequency, severity, and time of occurrence of hypokalemia and their relationship with vomiting was studied in 40 patients with acute theophylline poisoning. The mean peak theophylline concentration was 58 micrograms/mL (range, 21 to 115), and the mean nadir of serum potassium was 3.0 mEq/L (range, 2.1 to 3.9). In 85% of the patients, the nadir of serum potassium was less than 3.5 mEq/L; 45% had potassium concentrations of less than 3 mEq/L. The severity of hypokalemia correlated with peak serum theophylline concentrations (p less than 0.001). Hypokalemia was observed early in the course of the overdose (mean, 5 hours after ingestion or administration of theophylline). The nadir in serum potassium concentrations was more severe among 25 patients who presented to the emergency department within 6 hours of the overdose than among 13 patients who presented later (mean +/- SE, 3.0 +/- 0.1 mEq/L vs 3.4 +/- 0.1 mEq/L, p less than 0.01), despite similar admission serum theophylline concentrations in both groups (49 +/- 5 and 55 +/- 5 micrograms/mL, respectively; p = not significant). Spontaneous or ipecac-induced emesis occurred in 95% of the patients; however, hypokalemia preceded vomiting in 13 patients. Its severity was similar whether patients did or did not vomit before its occurrence. Hypokalemia is a frequent manifestation of acute theophylline poisoning, has a very early onset, and occurs independently of vomiting, suggesting an intracellular shift of potassium.     

Importance of blood-collection tubes in plasma lidocaine determinations.

In 25 clinical samples serum lidocaine concentrations fell from a mean of 6.5 +/- 2.1 mg/L (mean +/- SD) to 4.9 +/- 1.8 mg/L (p less than 0.001) when the blood sample was allowed to make contact with the stopper of the Vacutainer collection tube. In vitro experiments showed that this effect of the stopper occurred only with whole blood and was dependent on sample concentration. The plasma binding of lidocaine decreased from a normal value of 56% +/- 2.2 (mean +/- SD) to 28% +/- 2.2 (p less than 0.001) when exposed to the Vacutainer stopper. We conclude that a chemical leached from such stoppers displaces lidocaine from its plasma-binding sites and that the drug is then redistributed into the erythrocytes, producing spuriously low lidocaine concentrations in plasma or serum. Such artifacts are important in therapeutic drug monitoring and can lead to erroneous clinical decisions.     

Clinical pharmacology of timentin (ticarcillin and clavulanic acid)

Ticarcillin (4 gm) and clavulanic acid (0.1 gm) were simultaneously administered as timentin to patients with cancer as therapy for infections. The pharmacokinetics of both ticarcillin and clavulanic acid were studied in 15 patients after 30-minute and 2-hour intravenous infusions. The mean (+/- SD) ticarcillin plasma peak concentrations after the two infusions were 341 +/- 76 and 210 +/- 60 micrograms/ml. The plasma terminal t1/2 values of ticarcillin were 80 +/- 32 and 56 +/- 12 minutes. The AUCs were 631 +/- 189 and 601 +/- 230 mg/L X hr. The volumes of distribution of the area were 15 +/- 5 and 21 +/- 7 L and total clearances were 115 +/- 36 and 127 +/- 54 ml/min. The corresponding values for clavulanic acid after the infusions are as follows: mean peak concentrations, 5 +/- 1 and 4 +/- 1 micrograms/ml; plasma terminal t1/2 values, 84 +/- 24 and 74 +/- 36 minutes; AUCs, 11 +/- 3 and 11 +/- 6 mg/L X hr; volumes of distribution of the area, 22 +/- 3 and 32 +/- 6 L; and total clearances, 170 +/- 58 and 175 +/- 68 ml/min.