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Biomedical subjects

D L Roerig

Publications and source records attributed to D L Roerig.

At least 73 records · Page 4Linked to original sources
PubMed1976

Radioimmunuassay compared to thin-layer and gas--liquid chromatography for detecting methadone in human urine.

Radioimmunoassay was compared to thin-layer and gas--liquid chromatographic methods for detection of methadone in the urine of patients undergoing methadone maintenance therapy as treatment of heroin abuse. With urine samples known to contain methadone, 84% were positive by thin-layer chromatography as compared to 99% positives by the other two methods. This difference is attributed to the difference in sensitivity of the three methods. All three methods gave consistently positive results with urine samples from patients receiving 25 mg of methadone per day or more. With smaller daily doses the percentage of positive results obtained with thin-layer chromatography decreased. Analysis of urine samples not containing methadone showed no incidence of cross reaction of other drugs with the methadone radioimmunoassay. The methadone radioimmunoassay appears to be both sensitive and reliable; however, certain other factors limit its use as a primary screening method.

Chromatography, Gas↗
PubMed1976

Role of metabolism in the biliary excretion of methadone metabolites.

The biliary excretion of the major methadone metabolites was studied after the administration of purified 14C-labeled metabolites of methadone. The three methadone metabolites administered to rats were the pyrrolidine and pyrroline metabolites and the glucuronide conjugate of the hydroxylated pyrroline metabolite. We found that the excretion of 14C into bile was greater after administration of the metabolites which underwent fewer metabolic steps prior to biliary excretion. Phenobarbital pretreatment of rats increased the biliary excretion of 14C after the administration of the 14C-labeled pyrrolidine and pyrroline metabolites, both of which undergo further metabolism. Phenobarbital pretreatment did not change the biliary excretion of 14C-labeled glucuronide of the pyrroline metabolite which does not undergo further metabolism in the liver. Analysis of bile samples showed that the increased biliary excretion of 14C in phenobarbital-pretreated rats after administration of the labeled pyrrolidine and pyrroline metabolites was due primarily to increases in the biliary excretion of methadone metabolites which resulted from further in vivo metabolism of the injected metabolites. These data confirm our earlier suggestion (Roerig et al., Biochem. Pharmacol. 24: 355-362, 1975) that phenobarbital pretreatment increases biliary excretion of methadone metabolites by increasing hepatic metabolism of methadone. Furthermore, it can be concluded from these studies that metabolism is a rate-limiting process in the excretion of methadone metabolites in bile.

Animals↗
PubMed1975

Methods of identification and confirmation of abusive drugs in human urine.

A thin-layer chromatography (TLC) procedure is described to be used as the initial drug detection method for urine surveillance in a drug abuse treatment program. While the TLC method is sufficiently sensitive, it is prone to false-positive results. For this reason, two other drug detection methods (gas-liquid chromatography and radioimmunoassay) have been incorporated to confirm positive results obtained with TLC. The combined methodologies result in a urine surveillance procedure that is versatile, sensitive and highly reliable.

Amphetamine↗
PubMed1975

Comparison of radioimmunoassay with thin-layer chromatographic and gas-liquid chromatographic methods of barbiturate detection in human urine.

A radioimmunoassay (I) for barbiturates was compared with thin-layer chromatographic (II) and gas-liquid chromatographic (III) methods for barbiturate detection in human urine. Timed urine samples were obtained from volunteers who had ingested 100 mg of a barbiturate. I detected barbiturate in all urines tested up to 76 h after the dose, and III in all up to 52 h and in 90% up to 76 h. II detected barbiturates in 90% of all urine samples for only 30 h, after which is reliability declined. Glutethimide interfered with radioimmunoassay of barbiturate, producing false positives. I is sensitive, reliable, and fast, and lends itself to screening large numbers of urine samples for barbiturates. For routine urine surveillance, however, we found I to be less useful than II, which is still the method of choice. I has, however, proved to be an excellent method for confirming results of II.

Adult↗
PubMedDate not supplied

An interpretation of 14C-urea and 14C-primidone extraction in isolated rabbit lungs.

We measured the venous concentration versus time curves of 14C-urea and 14C-primidone after rapid bolus injections of a vascular reference indicator, fluorescein isothiocyanate dextran, and one of the two 14C-labeled indicators in isolated rabbit lungs perfused with Krebs-Ringer bicarbonate solution containing 4.5% bovine serum albumin at flow rates (F) of 6.67, 3.33, 1.67, and 0.83 ml/sec and with nearly constant microvascular pressure and total lung vascular volume. When we calculated the permeability-surface area product, PS, from the 14C-urea and 14C-primidone outflow curves using the Crone model, the estimates of the PS product were directly proportional to F. However, the fractional change in the PS with flow was different for the two indicators. We also estimated the PS from the same 14C-urea and 14C-primidone data using an alternative model that includes perfusion heterogeneity, estimated in a previous study, and flow-limited and barrier-limited extravascular volumes accessible to both urea and primidone. This model was able to fit the outflow curves of either 14C-urea or 14C-primidone at all four flows studied with one flow-independent PS for each indicator. The ability of the new model to explain the 14C-urea and 14C-primidone data with no flow-dependent change in PS suggests that a change in PS with F estimated using other models such as the Crone model is not sufficient for capillary surface area recruitment.

Animals↗
PubMedDate not supplied

Role of enterohepatic circulation in the analgesic action of 1-alpha-acetylmethadol in the rat.

The enterohepatic circulation of 1-alpha-acetylmethadol (LAAM) was investigated in the rat. Bile containing 3H-LAAM metabolites was collected from a biliary cannulated donor rat after administration of 3H-LAAM (5 mg/kg, 15 muCi/kg, sc) and infused into the intestine of a double biliary-cannulated recipient rat for 1 hr, and tritium excreted into the bile of the recipient rat was monitored. Within 1 hr after the end of infusion significant radioactivity was found in the bile of the recipient rat and by 10 hr 50% of the infused dose of 3H had been re-excreted into bile. The contribution of enterohepatic circulation of LAAM metabolites to the analgesic action of LAAM was also assessed. Pretreatment of rats with neomycin sulfate was used as a method of decreasing enterohepatic circulation of biliary glucuronide conjugates of LAAM metabolites, and such pretreatment had no effect on LAAM analgesia (6 mg/kg) measured by the hot-plate method. In rats with a biliary fistula, a situation in which enterohepatic circulation was completely eliminated, the analgesic response to a dose of LAAM (6 mg/kg, sc) was not different from sham-operated control group. The above findings indicate that enterohepatic circulation of LAAM metabolites does not contribute to the intensity or duration of LAAM analgesia.

Analgesics↗
PubMedDate not supplied

Uptake and efflux of 1-alpha-acetylmethadol (LAAM) and methadone in the isolated perfused rat lung.

The pulmonary uptake of 1-alpha-acetylmethadol (LAAM) and methadone was studied during a single pass through the isolated perfused rat lung (IPL). The IPL was perfused for 10 min with perfusate containing various concentrations of one of the radiolabeled drugs, followed by a 30-min drug-free perfusion and the amount of radioactivity in the pulmonary venous effluent was used to estimate uptake and efflux of the drugs with time. Both drugs were extensively taken up by the IPL; however, LAAM uptake was significantly greater than that of methadone. The amount of each drug taken up was a nonlinear function of concentration in the perfusate, suggesting saturability of the major uptake processes. During drug-free perfusion LAAM and methadone previously accumulated were released from the lung at two different efflux rates; however, a third, more rapid efflux process for methadone was also evident. The total venous effluent collected during the drug-free perfusion contained a significantly greater fraction of the accumulated methadone as compared to LAAM. Calculation of the total amount of each drug effluxable at the observed rates indicated that another pool for both drugs existed in the lung that did not efflux at an observable rate. The accumulated LAAM remaining in this "slowly effluxable pool" was significantly greater than methadone. These data demonstrate a greater pulmonary uptake and tissue sequestration of LAAM as compared to methadone, and may be one of the contributing factors in the persistence of LAAM and its active metabolites in the body.

Animals↗
PubMedDate not supplied

Brain and plasma levels of methadone and their relationships to analgesic activity of methadone in rats.

The levels of methadone in brain and plasma of rats after acute administration of several different doses of methadone were measured at several time points and relationships to analgesic activity were examined. Both brain and plasma levels of methadone as well as the analgesic activity of methadone, expressed as analgesic area and as percentage of maximum possible effect, were all increased by increasing dosage. All these measurements dropped rapidly after reaching the peak levels 30 min after administration of methadone. At the time of maximal analgesia, the analgesic effect of methadone was quantitatively related to both brain and plasma levels of methadone with 50% of the analgesic maximum possible effect corresponding to the concentrations of 1.44 nmol/g and 0.52 nmol/ml of methadone in brain and plasma, respectively. Our data suggest that measurement of changes in the plasma concentration of methadone at the time of maximal analgesia reflects changes in the brain concentration of methadone and may provide an index of changes in the analgesic effect of methadone.

Analgesics, Opioid↗
PubMedDate not supplied

Uptake of l-alpha-acetylmethadol (LAAM) and its analgesically active metabolites, nor-LAAM and dinor-LAAM, in the isolated perfused rat lung.

The pulmonary uptake of l-alpha-acetylmethadol (LAAM) and its major analgesically active metabolites, nor-LAAM and dinor-LAAM, was studied during a single pass through the isolated perfused rat lung (IPL). The radiolabeled drugs were infused into the IPL for 10 min followed by a 30-min drug-free perfusion. All three drugs were extensively taken up into the IPL; however, dinor-LAAM, the least lipophilic, accumulated to the greatest extent. Their rates of efflux from the IPL with time could be described by the sum of three exponentials and 20-25% of each compound accumulated in a "slowly effluxable pool," suggesting a highly sequestered pool of drug in the lung. These findings suggest that tissue sequestration of the active metabolites is equal to or greater than LAAM itself. Such tissue sequestration could limit the sequential metabolic activation or inactivation, and serve as a reservoir of the active compounds. These factors favor the persistence of LAAM and its active metabolites in the body, thus prolonging the opiate-like effects after LAAM administration. The data also indicated that the relationship between drug basicity or lipophilicity and extent of uptake is complex and it is difficult to associate a particular physicochemical property with the extent or character of pulmonary drug uptake.

Animals↗
PubMedDate not supplied

Effect of plasma protein binding on the uptake of methadone and diazepam in the isolated perfused rat lung.

The pulmonary uptake of the basic (pKa 9.1) lipophilic amine (methadone) and a nonbasic (pKa 3.4) lipophilic amine (diazepam) was compared in a single pass isolated perfused rat lung (IPL) preparation. The radiolabeled drugs were infused into the IPL for 10 min followed by a 30-min drug-free perfusion. If the perfusate (Krebs-Ringer bicarbonate buffer) contained 4.5% bovine serum albumin, the rapid and extensive uptake observed for methadone (32.4% of infused amount) was similar to that reported for other basic lipophilic amines. Uptake of the nonbasic diazepam was slight (3.4% of infused amount). These results are consistent with the idea that basic amines accumulate in lung tissues to a great extent. However, if the bovine serum albumin was omitted from the perfusate, diazepam uptake in the IPL increased about 10-fold while methadone uptake increased only slightly. This observation, together with the extensive binding of diazepam to plasma albumin, suggested that plasma protein binding was a major factor in limiting the pulmonary accumulation of this nonbasic lipophilic amine. Since many nonbasic drugs are known to have a high affinity for plasma albumin, the observed dependence of pulmonary drug accumulation on basicity of the amine may be related to the plasma protein binding as well as the characteristics of the interaction of amines with pulmonary tissue.

Animals↗