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Objective In the management of patients with suspected acute drug poisoning, a screening test using the patient's urine is usually performed. The Triage DOA ® and INSTANT-VIEW M-1 ® kits are two commonly used point-of-care screening kits in Japan. However, the relationship between the results of these screening kits and the blood concentration of the poisoning drug is not clear. In this study, we evaluated which kit is more useful for acute drug poisoning screening based on a comparison of their results with the results of a serum drug analysis. Methods This prospective cross-sectional study investigated all patients with acute drug poisoning admitted to a general hospital in Tokyo, Japan, over a nine-month period. The Triage DOA ® and INSTANT-VIEW M-1 ® screening kits were used, and a qualitative serum analysis was conducted simultaneously in all cases. We compared the kits for use in screening patients with acute drug poisoning and evaluated the utility of the kits. Results For the 117 patients enrolled in this study, the 2 kits showed different sensitivities to benzodiazepines (Triage ® , 78.6%; INSTANT-VIEW ® , 90.5%). Both kits showed high sensitivity to barbiturates (Triage ® , 87.0%; INSTANT-VIEW ® , 91.3%) but low sensitivity to tricyclic antidepressants (Triage ® , 25.0%; INSTANT-VIEW ® , 45.8%). Conclusion Because the sensitivity varies depending on the kind of drug, it is difficult to discuss the superiority of these kits. However, this study compared the results of two types of urinary drug screening kits with the results of qualitative analysis of drugs in serum as a gold standard, providing important reference data.

Zoliflodacin is a novel spiropyrimidinetrione with activity against bacterial type II topoisomerases that inhibits DNA biosynthesis and results in accumulation of double-strand cleavages in bacteria. We report results from two phase 1 studies that investigated the safety, tolerability, and pharmacokinetics (PK) of zoliflodacin and absorption, distribution, metabolism, and excretion (ADME) after single doses in healthy volunteers. In the single ascending dose study, zoliflodacin was rapidly absorbed, with a time to maximum concentration of drug in serum ( T max ) between 1.5 and 2.3 h. Exposure increased dose proportionally up to 800 mg and less than dose proportionally between 800 and 4,000 mg. Urinary excretion of unchanged zoliflodacin was <5.0% of the total dose. In the fed state, absorption was delayed ( T max , 4 h), accompanied by an increase in the area under the concentration-time curve (AUC) at 1,500- and 3,000-mg doses. In the ADME study (3,000 mg orally), the PK profile of zoliflodacin had exposure (AUC and maximum concentration of drug in serum [ C max ]) similar to that of the ascending dose study and a median T max of 2.5 h. A total of 97.8% of the administered radioactivity was recovered in excreta, with urine and fecal elimination accounting for approximately 18.2% and 79.6% of the dose, respectively. The major clearance pathway was via metabolism and elimination in feces with low urinary recovery of unchanged drug (approximately 2.5%) and metabolites accounting for 56% of the dose excreted in the feces. Zoliflodacin represented 72.3% and metabolite M3 accounted for 16.4% of total circulating radioactivity in human plasma. Along with the results from these studies and based upon safety, PK, and PK/pharmacodynamics targets, a dosage regimen was selected for evaluation in a phase 2 study in urogenital gonorrhea. (The studies discussed in this paper have been registered at ClinicalTrials.gov under identifiers NCT01929629 and NCT02298920.)., (Copyright © 2018 American Society for Microbiology.)

Urine drug testing (UDT) has become an essential component in the management of patients prescribed opioid analgesics for the treatment of chronic non-malignant pain. Several laboratory methods are available to monitor adherence with the pharmacological regimen and abstinence from illicit or unauthorized medications. Immunochemical screening methods are rapid and economical, but they have limitations, including lack of specificity, and confirmatory methods are often necessary to verify presumptive positive results. We analyzed the results of confirmatory assays in an outpatient setting to determine the predictive value of presumptive positive urine drug screen results using an automated immunoassay for eight common drugs or drug classes. Positive predictive values (PPVs), in descending order, were as follows: cannabinoids (100%), cocaine (100%), opiates (86.8%), benzodiazepines (74.6%), oxycodone (67.6%), methadone (44.1%) and amphetamines (9.3%). The number of positive barbiturate results was too small to be included in the statistical analysis., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The abuse of barbiturate drugs is widespread, and the development of methods for their efficient separation and quantification is needed. Three barbiturate drugs were preconcentrated and determined by in-line solid-phase extraction (SPE) capillary electrophoresis (CE) in urine samples. Different parameters affecting preconcentration were evaluated, such as the sample pH, the volume of the elution plug and the sample injection time. This strategy enhanced the detection sensitivity in the range of 170- to 1840-fold, compared with normal hydrodynamic injection. The method provides limits of detection (LODs) for standard samples in the range of 0.5 to 5 ng/mL with good repeatability and reproducibility values. The LODs obtained for urine samples were in the range of 5 to 60 ng/mL. The validation with human urine samples spiked with the studied compounds demonstrated the applicability of the optimized method. This method provides a reproducible and sensitive analysis of urine samples in the determination of barbiturates drugs.

Urine drug testing is an important tool that is commonly used to assess patient compliance with prescription regimens. Point-of-collection immunoassay devices allow for timely availability of laboratory test results to guide therapy during the same office visit. Two waived immunoassay-based urine drug screen cups were evaluated in this study. The NexScreen cup and the DrugCheck Waive RT cup claim to detect 10-12 drug classes of commonly used and/or abused drugs. This study included a sensitivity and precision challenge with 4-6 replicates at concentrations 0-150% of the manufacture's claimed cutoff, using drug-free urine spiked with purified reference standards. The stability of test results was evaluated by reading the results at intervals between five and 1,440 min. Specificity was evaluated by parallel comparison of pooled patients' specimens, representing 56 patients and 41 known drug compounds. When comparing results to validated liquid chromatography-mass spectrometry results, false positives were observed in the NexScreen cups for benzodiazepine, methamphetamine, methadone, opiates and tricyclic antidepressant tests, but there were no false negatives. The DrugCheck Waive RT cups showed false negative results for barbiturates and opiates, but no false positives. Overall, the NexScreen cup demonstrated better sensitivity than claimed, whereas the sensitivity of the DrugCheck Waive RT cup did not meet claims.

The availability of point-of-care (POC) medical devices for drug testing has surged. Reduction in turnaround time, and hence, rapid results are attractive, particularly to acute care facilities, rehabilitation facilities and specialized clinics such as pain management clinics. Here we describe our validation results for the Integrated E-Z Split Key Cup II, a low-cost, rapid urine test that utilizes competitive immunoassay technology to detect 12 drugs or drug classes of commonly abused drugs. Positivity is based on the absence of a colored band at a labeled portion of the detection strip; a negative result produces a distinct, colored band. Using reagent-grade standards, the apparent cut-off for each of the drugs was challenged. The stability of the results was monitored over time. Five urine samples known to be negative for all drug categories and 24 patient samples confirmed positive for a total of 95 drugs and/or drug metabolites claimed to be detected by the device were tested. Adulterants and potential cross-reacting compounds were also evaluated. One false-positive result for benzodizepines was observed. One false-negative result for barbiturates was observed, but was resolved. Overall, the cups demonstrated excellent sensitivity, specificity, and diagnostic efficiency for all drugs represented.

A method was developed for the quantitative analysis of 30 drugs of abuse and their metabolites in urine, including opiates, barbiturates, amphetamines, cocaine, cannabinoids, phencyclidine, methadone, and benzodiazepines. This method uses solid-phase extraction (SPE) on an Oasis HLB column followed by liquid chromatography-tandem mass spectrometry. Analytes were quantified by multiple reaction monitoring with the deuterated analogues as internal standards, using an atmospheric pressure ionization-electrospray interface. The method was validated by examining specificity, precision, accuracy, linearity, recovery, reproducibility, and detection limits. The limits of detection ranged from 9 pg/mL to 2.29 ng/mL in urine depending on the analyte. The SPE procedure was automated on a RapidTrace workstation to increase analytical throughput, and the results obtained via automated SPE were compared to those obtained by manual SPE to examine carryover effect, precision, accuracy, recovery, and reproducibility. To evaluate method performance, 108 urine samples were collected anonymously and tested for the presence of these drugs.

The pressure to reduce the cost of analytic testing makes it tempting to discontinue routine confirmation of urine specimens positive for drugs of abuse by immunoassay. Beyond the economic motivation, the requirement for confirmation should be driven by the positive predictive value of the screening tests. We have quantitated positive predictive values of our screening immunoassays in a large metropolitan Veterans Affairs Medical Center. We reviewed the confirmatory rate of urine specimens positive for drugs of abuse with Beckman Synchron reagents from June 1998 to June 1999 and tabulated the false-positive screening rate. There were 175 instances of false-positive screens during the 13 months we analyzed. Positive predictive values ranged from 0% (amphetamine) to 100% (THC). We determined that the low positive predictive value of the amphetamine assay in our laboratory was primarily due to the use of ranitidine (Zantac). Urine specimens containing greater than 43 microg/mL ranitidine were positive in our amphetamine assay. This concentration is routinely exceeded in our patients taking ranitidine. In our clinical and analytic setting, the Beckman THC assay did not require confirmation. The positive predictive values of the Beckman opiate, cocaine, barbiturate, propoxyphene, and methadone immunoassays dictate routine confirmatory testing in specimens that screen positive for these substances. Finally, because of its extreme sensitivity to ranitidine, the Beckman amphetamine assay has little utility in our laboratory setting.

The performance of the new fluorescence polarization immunoassay reagents Cassette COBAS INTEGRA Serum Benzodiazepines assay (SBENZ) and Cassette Serum Barbiturates assay (SBARB) was evaluated as compared to other immunoassays (Abbott TDx Serum Benzodiazepines, Abbott TDx Urine Benzodiazepines, Behring EMIT Serum Benzodiazepines, Abbott ADx Serum Barbiturates, Behring EMIT Serum Barbiturates, and the COBAS INTEGRA Barbiturates (BARB) urine assay) and gas chromatography-mass spectrometry (GC-MS). Recoveries of nordiazepam and secobarbital using the SBENZ and SBARB assays, respectively, were equivalent for serum, plasma, and urine. Cross-reactivities of structurally related benzodiazepines, barbiturates, and their metabolites were very similar in serum and urine for the SBENZ and SBARB assays. Precision was within 5.4% for SBENZ serum and within 11% from 10 to 100 ng/mL for urine. Precision was within 5% for SBARB serum and within 7% from 136 to 277 ng/mL for the urine application. The standard curves for SBENZ and SBARB were stable for at least 16 weeks with the reagents stored open on the COBAS INTEGRA analyzer. Clinical comparison of the SBENZ serum assay indicated an increased pickup rate, as confirmed by GC-MS, compared to TDx and EMIT. The diagnostic sensitivities of the SBENZ serum application, TDx, and EMIT versus GC-MS were 100%, 89%, and 36%, respectively. The diagnostic specificities were 71%, 79%, and 100%, respectively. The diagnostic sensitivities of the SBENZ urine application and TDx versus GC-MS were 100% and the diagnostic specificities were 88%. The increased positive pick-up of the SBENZ assay compared to the other immunoassays is most probably due to the difference in the limit of detection (LOD) and the increased cross-reactivity for the low-dose benzodiazepines. Clinical comparison of the SBARB serum assay indicated an increased positive pick-up rate, as confirmed by GC-MS. The diagnostic sensitivities of the SBARB serum application, ADx, and EMIT versus GC-MS were 96%, 65%, and 35%, respectively. The diagnostic specificities were all 100%. The diagnostic sensitivities for the SBARB urine application and BARB versus GC-MS were all 100%, and the diagnostic specificities were all 91%. The SBENZ and SBARB kits demonstrated increased sensitivity for the detection of benzodiazepines and barbiturates in both serum and urine compared to the other immunoassays.

Broad-spectrum drug screening requires that all relevant substances be isolated, detected, and identified, regardless of their structure and/or polarity. To this end, systematic solid-phase extraction (SPE) approaches for drug isolation from biological fluids are required. Because speed and cost effectiveness are key issues in analytical toxicology, we have evaluated a disc-format extraction device for this purpose and compared the latter with an existing packed-bed column-format method. The discs were SPEC.PLUS.C18AR/MP3 cartridges with 10-mL solvent reservoirs, providing hydrophobic and cation exchange interactions. Blank human urine was spiked at 2 microg/mL with a selection of acidic, neutral, and basic drugs representing a variety of relevant drug classes. Urine specimens (2 mL) were diluted with 2 mL 0.1 M phosphate buffer (pH 5.0) and then applied to the preconditioned disc. Washing was done with 1 mL water. Acidic and neutral drugs were eluted with 1 mL ethyl acetate/acetone (1:1), and basic drugs were eluted with 1 mL ammoniated ethyl acetate. The eluates were collected separately, evaporated down to about 0.1 mL, and analyzed by gas chromatography-flame-ionization detection to check cleanliness, recoveries, and reproducibilities. The discs showed good extraction properties for all drugs and were easy to handle. Recoveries were 75-100% with coefficients of variation of around 5%. The resulting eluates showed only a few matrix interferences. As compared to our standard SPE method with packed-bed columns, the disc procedure allowed reductions in elution volumes and total processing time of approximately 60-65%.

It is now accepted that drug misuse is a large and growing problem in the United Kingdom, some estimates of the number of regular illicit drug users being as high as three million. The aim of this paper is to provide insight into the methods used to detect drug misuse. The strategy adopted by one laboratory is described and methods of screening for, and identification of, a wide range of compounds are provided. No claim is made that this is the best approach or that the list of drugs detected is comprehensive; the range of drugs encountered is always increasing and the lists are constantly updated. It is hoped that users of toxicology laboratory services will gain an appreciation of the capabilities and limitations of the techniques available; and that those who may wish to provide such a service will find the necessary information in a readily accessible format.

A high-performance liquid chromatographic method has been developed for the forensic analysis of 10 frequently used barbiturates (BARs) (allobarbital, amobarbital, barbital, cyclobarbital, hexobarbital, metharbital, pentobarbital, phenobarbital, secobarbital and thiopental) using a recently developed reversed-phase column packed with 2-micron particles. The results show that the new ODS column packing gives higher sensitivity and a shorter analysis time than the conventional ODS column packing when applied to the analysis of biological samples.

To clarify the chemical nature and pathophysiological significance of an endogenous, specific Na-pump inhibitor, extracts of various tissues have been examined. The activities were extracted by an Amberlite XAD-2 adsorbent and fractionated by high-performance liquid chromatography (HPLC) on an ODS column. Among many tissues and fractions tested, the extract of pig urine has been found to contain a large amount of 86Rb uptake inhibitory activities. The strongest inhibitory activity for 86Rb influx into erythrocytes also exhibited a cross-reactivity with anti-ouabain antibodies. This activity has been purified to homogeneity using five steps of reverse-phase HPLC. Although most of the dose-response curves for this purified Na-pump inhibitor, designated as uroxin, in the various assay systems paralleled those of ouabain and the inhibitor purified from bovine adrenal glands (designated as adrexin C), the cross-reactivity curve with anti-ouabain antibodies did not. The retention time of uroxin on an ODS HPLC column was also different from that of digoxin, ouabain, or adrexin C. 1H nuclear magnetic resonance spectroscopic study suggests that uroxin is a novel Na-pump inhibitor that is structurally different from any of the known cardiotonic steroids or the substances previously reported to exhibit Na-pump inhibitory activity. Thus, uroxin may be a new type of endogenous regulator for the Na pump.

1 Hexobarbitone plasma kinetics were determined in six healthy volunteers, who received 500 mg hexobarbitone orally. In addition urinary excretion rate and cumulative excretion were measured of its three major metabolites: 3'-hydroxyhexobarbitone, 3'-ketohexobarbitone and 1,5-dimethylbarbituric acid. 2 The mean plasma elimination half-life of hexobarbitone was 3.7 +/- 0.9 h (n = 6). Assuming complete absorption, the volume of distribution and the metabolic clearance were 81.3 +/- 20.5 1 and 16.4 +/- 2.9 1/h, respectively. The mean maximal plasma concentration was 7.1 +/- 2.1 micrograms/ml and was reached 1.2 +/- 0.4 h after drug administration. 3 3'-Hydroxyhexobarbitone and 3'-ketohexobarbitone, which are products of allylic side-chain oxidation of hexobarbitone, were excreted in 24 h to the extent of 4.7 +/- 1.3 and 32.1 +/- 11.9% of the dose, respectively. In the same period, 1,5-dimethylbarbituric acid, which is the end product of the epoxide-diol pathway, was excreted to 18.0 +/- 7.8% of the dose. The ratio of the sum of 3'-hydroxy- and 3'-ketohexobarbitone vs 1,5-dimethylbarbituric acid excreted varied with time and amounted ultimately in 24 h urine to 2.3 +/- 1.0. 4 The half-lives of 3'-hydroxyhexobarbitone and 1,5-dimethylbarbituric acid, calculated from their renal excretion rate curves, amounted 5.2 +/- 0.9 and 6.6 +/- 1.3 h and were significantly longer than the half-life of hexobarbitone in plasma. The half-life of 3'-ketohexobarbitone was 4.2 +/- 0.8 h. The maximum excretion rate of 1,5-dimethylbarbituric acid was reached at 7.7 +/- 1.0 h after administration of hexobarbitone. 3'-Hydroxy- and 3'-ketohexobarbitone were excreted with a maximal rate at 2.2 +/- 0.8 and 2.8 +/- 0.4 h respectively.

1 Thirty-three patients with no evidence of endocrine disease, hepatic or renal insufficiency or sleep disorders, were classified in groups 1 to 4 in order of increasing of percentage of ideal body weight (IBW) respectively: less than 90% of IBW, 90--120%, 120--180%, and greater than 180% of IBW. After oral administration of 200 mg butobarbitone, concentration of the intact drug was measured by gas liquid chromatographic assay in urine samples collected during 72 h and at three times in blood. 2 A highly significant negative relationship was found between the cumulative excretion of butobarbitone with urine and the logarithm of the percentage of IBW. In contrast for a given weight, excretion of the drug with urine was found to be weakly correlated with the diuresis. 3 The cumulative urinary elimination of butobarbitone was significantly different between the groups studied, except of the difference between the group 2 and 3 of the patients. No significant difference was found between the renal clearances of butobarbitone in the four groups of subjects. 4 We conclude that redistribution of butobarbitone into adipose tissues can explain the obtained results and that obesity modifies the pharmacokinetics of the drug.

The ability of morphine to block ovulation in animals prompted investigation of the frequency and mechanisms of menstrual abnormalities in women addicted to narcotic analgesics. Menstrual histories obtained from 76 former heroin addicts receiving daily methadone maintenance revealed that more than one-half of these women had experienced menstrual abnormalities while taking heroin or methadone. In order to determine the specific physiologic effects of narcotic analgesics on reproductive function, detailed endocrinologic studies were carried out in seven of these patients who complained of amenorrhea or irregular menses while receiving methadone. Four of the seven women manifested abnormalities of the control of gonadotropin secretion. Three of these four failed to exhibit cyclic gonadotropin release, as evidenced by an absence of increased levels of follicular phase follicle-stimulating hormone, midcycle gonadotropin peaks or luteal phase progesterone increments. In the fourth patient a prolonged follicular phase (30 days) of the menstrual cycle was detected. One of these four patients also had low basal gonadotropin levels and failed to exhibit luteinizing hormone increments greater than control levels in response to ethinyl estradiol (positive feedback). The remaining three women exhibited normal patterns of gonadotropin secretion during the observation period. In these women, menstrual bleeding occurred in response to withdrawal from luteal phase (10 to 20 ng/ml) progesterone levels and to exogenous ethinyl estradiol, suggesting normal uterine responsivity to progesterone and estrogen. Although not documented, it is likely that oligo-ovulation was the cause of the irregular menses in these three patients. Amenorrhea is commonly associated with methadone ingestion or heroin addiction and appears to be related to an alteration of the hypothalamic mechanisms controlling gonadotropin secretion. Tolerance to these effects of methadone may develop after chronic ingestion.

The techniques used to analyse 212 "under-the-limit" drink-driving blood and urine specimens for drugs during a 3-year period (1982-85) in Northern Ireland are described. In all of these specimens (representing 15% of all below-limit cases) either the police surgeon who carried out the clinical examination, or the police, strongly suspected that drugs may have been a contributory factor in driving impairment, considering the lower than expected alcohol concentration. Thirty-eight (18%) samples were found to contain significant drug(s). Benzodiazepines were the most frequently encountered group of drugs (87% of all positive cases) with diazepam being that most frequently encountered (18 cases). The analytical procedures were radioimmunoassay, gas chromatography using nitrogen selective and electron capture detection along with high performance liquid chromatography (HPLC) using ultra-violet detection. Drugs and their metabolites were identified using a mixture of these techniques along with GC/MS where possible. The usefulness of HPLC coupled with a rapid-scanning diode-array spectrophotometer is also demonstrated, the technique being particularly useful in the analysis of some of the more "difficult" benzodiazepines (e.g. lorazepam, temazepam, nitrazepam) not directly amenable to gas chromatography without derivatisation.

Urine lipoperoxides were measured, as the malondialdehyde-thiobarbituric acid adduct, by "high performance" liquid chromatography in men who tested positive for any of the common "drugs of abuse." Urine malondialdehyde concentrations were within the reference range in those urines containing barbiturates and amphetamines. On the other hand, significant urine malondialdehyde elevations were associated with those testing positive for marijuana (p less than 0.005), cocaine, opiates, benzodiazepines, and in those urines containing multiple drugs (p less than 0.001). The mechanism of tissue damage by these drugs is not necessarily by lipid peroxidation, since their primary toxic effects might result in cellular injury by an alternative mechanism; the observed increased lipid peroxidation could be a secondary phenomenon following tissue injury.

1. Sodium amylobarbitone was given by intravenous infusion to six patients with chronic renal insufficiency and to six healthy volunteer subjects. Serum concentrations of amylobarbitone and its major metabolite hydroxyamylobarbitone were measured by a gas chromatograph method.2. The serum concentrations of amylobarbitone were consistently lower in the patient group than in the control group and the concentration half time was shorter (0.10>P>0.05); the 48 h urinary excretion of hydroxyamylobarbitone was reduced (P<0.001) and the serum concentrations of hydroxyamylobarbitone were consistently raised.3. When two patients were given 200 mg of sodium amylobarbitone daily over five consecutive days the serum concentration of hydroxyamylobarbitone rose steadily to a maximum of about 8 mug/ml. The serum concentrations in two healthy control subjects did not exceed 0.5 mug/ml.4. Three parallel tests of cognitive function (Otis matched test forms A, B and C) were given to 16 control patients and to 12 amylobarbitone-treated patients. Significant impairment of performance was observed in test B (P<0.001) at a time when amylobarbitone only could be detected in the patients' serum, and in test C (P<0.001) when amylobarbitone concentrations were very low (0.52+/-0.08 mug/ml+/-SEM) but hydroxyamylobarbitone concentrations were still high (3.30+/-1.23, mug/ml+/-SEM).5. There was a strong (r=-0.71) and significant (P<0.01) negative correlation between the performance in test C and the serum concentration of hydroxyamylobarbitone. It is concluded that hydroxyamylobarbitone has cerebral depressant effects in man.

1. A single dose of amylobarbitone (3.23 mg/kg) was given by intravenous injection to each of ten healthy controls and two groups of five patients with chronic liver disease. A curve of serum amylobarbitone concentration against time was prepared for each subject and the proportion of the serum amylobarbitone bound to protein determined. The urinary excretion of the metabolite hydroxyamylobarbitone, ethyl (3 hydroxyisoamyl) barbituric acid was measured.2. The degree of protein binding of serum amylobarbitone was reduced in the five patients (group I) with abnormally low concentrations of albumin in serum (<3.5 g/100 ml) but was normal in the five patients (group II) with normal serum albumin concentrations (>3.5 g/100 ml).3. The equation for a double exponential decay was fitted to the concentration/time curves for amylobarbitone free in the serum water. The mean intercepts and rate constants were used to calculate the dimensions of mathematical models based on a two compartment open system.4. The five patients (group I) who had abnormally low concentrations of albumin in serum showed impairment of amylobarbitone metabolism; the rate constant beta(h(-1)) for the second exponential decay of serum amylobarbitone concentration was reduced (P<0.01), the urinary excretion of hydroxyamylobarbitone was reduced (P<0.001) and the mean serum water clearance (C, ml/min) representing amylobarbitone elimination by metabolism was reduced.5. The five patients (group II) who had normal concentrations of albumin in serum showed no impairment of amylobarbitone metabolism. Within the total patient group there were strong and significant positive correlations between the serum albumin concentration and each of the indices of the rate of amylobarbitone metabolism.6. Both patient groups showed an increase in the first dispositional rate constant alpha(h(-1)) and in the clearance (C(t) ml/min) representing transfer between central and peripheral compartments. The physiological basis for this observation is uncertain.7. The clinical response to the single intravenous dose of amylobarbitone was not significantly greater (P=0.11) in the patient group (I) with slow amylobarbitone metabolism than in the patient group (II) with a normal rate of amylobarbitone metabolism.