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Biomedical subjects

J R Lawrence

Publications and source records attributed to J R Lawrence.

At least 91 records · Page 5Linked to original sources
PubMed1979

The protein binding of methotrexate by the serum of normal subjects.

The protein binding of methotrexate by serum from eight normal volunteers was assessed by continuous ultrafiltration at pH 7.4 and 37 degrees C. Methotrexate concentrations were measured by radioimmunoassay and the data analysed by the method of Scatchard. The major binding protein was albumin which bound 87.3% of the drug in serum. Analysis of the Scatchard plots indicated two distinct groups of binding sites. Class I was found to have 0.16 +/- 0.05 (S D) binding sites with an intrinsic association constant of 71.15 +/- 35.98 (S D) X 10(4) M-1: Class II had 2.01 +/- 0.93 (S D) binding sites and and affinity of 0.18 +/- 0.15 X 10(4) M-1. No great change in the percentage of methotrexate bound occurred until the total concentration of the drug exceeded 50 muMol 1-1.

Blood Proteins↗
PubMed1979

Idiopathic edema.

Explore the source record for details and available documents.

Body Water↗
PubMed1979

Alterations of phenytoin protein binding with in vivo haemodialysis in dialysis encephalopathy.

Protein binding of phenytoin was assesed in one patient with dialysis encephalopathy before and after haemodialysis. Phenytoin concentrations were measured by radioimmunoassay and continuous ultrafiltration was used to assess phenytoin binding. At a serum concentration of 60 micromol.1-1 the percentage of phenytoin bound to serum albumin was considerably lower in the patient serum (79.95% predialysis; 92.09% postdialysis) than that in three normal sera (97.90 +/- 0.17%). Analysis of Scatchard plots indicated two classes of binding sites. In class I both the affinity and capacity for binding phenytoin were reduced in the pre and post-dialysis serum, whereas in class II the capacity of the uraemic serum was increased although the intrinsic association constant was greatly reduced. It was concluded that in vivo haemodialysis is associated with large fluctuations in the protein binding of phenytoin, in which the concentration of endogenous dialysible metabolites are strongly implicated.

Adult↗
PubMed1979

Enhancement of methotrexate absorption by subdivision of dose.

A comparison was made in fasting patients between a single 100 mg oral dose of methotrexate formulated as its sodium salt in a palatable syrup and the same total quantity of drug administered in four divided doses of 25 mg taken at 2-h intervals. Allocation to the order of these treatment schedules was on a random basis. The area under the serum methotrexate concentration-time curve until 50 h was found to be considerably greater after the divided dose regimen, the mean ratio AUC 25 mg x 4/AUC 100 mg being 1.86 (+/- 0.90). There was no significant difference in peak serum methotrexate concentrations or methotrexate half-life estimates between the two regimens, however. The results of this study are consistent with saturation of an intestinal transport process when methotrexate is administered orally in a single large dose.

Half-Life↗
PubMed1979

Bioavailability of methotrexate: implications for clinical use.

The absorption of oral methotrexate in syrup form has been compared in six patients with that of an identical IV dose (50 mg/m2). There was variable absorption amongst the group with respect to maximum levels achieved and the time taken to reach those levels. The area under the time-concentration curve was always smaller when the drug was given orally than after IV administration. A total of 33 patients receiving methotrexate for a variety of tumour types were followed for response to treatment and toxicity. A significantly longer methotrexate half-life (t1/2) was found in nine partial responders (9.2 +/- 1.6 h) than in the nonresponders (3.8 +/- 0.7 h). Severe methotrexate toxicity was not seen though occasional mucositis, conjunctivitis, and diarrhoea occurred in seven patients. The side effects could not be predicted from the dose, the bioavailability data, or the serum creatinine. Measurements of serum and urine methotrexate levels are useful in the assessment of absorption and bioavailability of the drug the prediction of tumour response.

Administration, Oral↗
PubMed1979

Effect of acute alcohol intoxication on the metabolism and plasma kinetics of chlordiazepoxide.

1. The metabolism and plasma kinetics of chlordiazepoxide have been determined in a group of volunteers and in a group of patients with acute alcohol intoxication. 2. Using the SAAM 26 non-linear least squares fitting programme, all chlordiazepoxide plasma concentration v time data following oral administration could be analysed in terms of a one-compartment open model with metabolic conversion of chlordiazepoxide to desmethylchlordiazepoxide. 3. Acutely intoxicated patients showed a prolonged elimination of chlordiazepoxide and a reduced clearance when compared with alcohol-free volunteers. The elimination of desmethylchlordiazepoxide, on the other hand, appeared to be faster in the alcoholics. 4. Alcohol exerts significant effects on the metabolism of chlordiazepoxide in acutely intoxicated patients.

Adult↗
PubMed1979

Serum, tear and salivary concentrations of methotrexate in man.

1. Methotrexate handling has been studied in four patients with psoriasis and eleven patients with neoplastic disease. 2. Methotrexate levels in serum, tears and saliva were measured by radioimmunoassay while protein binding studies were performed by continuous ultrafiltration. 3. There was a close correlation between methotrexate concentrations in tears and serum (P less than 0.001, r = 0.714). Parotid salivary and serum methotrexate levels were similarly correlated (P less than 0.001, r = 0.557) but not mixed salivary and serum levels (P greater than 0.1, r = 0.232). 4. The mean protein binding was 95.11% +/- 2.26 (s.d.) while the ratio of methotrexate levels in tears to the free serum methotrexate level was 1:1.04. The corresponding parotid salivary level: free serum level ratio was 1:18.11. 5. No relationship could be determined between the methotrexate levels in tears and conjunctivitis observed in some of the patients under study.

Humans↗
PubMed1979

Systemic absorption of topically applied chloramphenicol eyedrops.

Five children under the age of 9 years had topical chloramphenicol drops administered 2-hourly to each eye for 5 to 7 days. Systemic absorption was not detected by 2 sensitive assays for the drug. The hazards of topical chloramphenicol and reports in the current literature are discussed.

Absorption↗
PubMed1979

Systemic absorption of topical and subconjunctival gentamicin.

Ten patients received ocular gentamicin therapy topically or subconjunctivally. Systemic absorption was not detected after topical use but was detected after subconjuctival administration. The relative safety of ocular gentamicin therapy is discussed and the literature is reviewed.

Absorption↗
PubMed1978

An alternative method of assessing changes in salivary flow: comparison of the effects of clonidine and tiamenidine (HOE 440).

An established method for collecting uncontaminated parotid saliva has been applied to assessment of salivary flow rate. Following single doses of 0.3 mg clonidine and 1.0 mg tiamenidine (HOE 440) changes in blood pressure, heart rate, sedation (assessed by a self-rating scale) and salivary flow were followed in nine normal subjects. Both drugs produced a fall in systolic and diastolic blood pressure, sedation, depression of salivary flow and a lowering of heart rate. These changes were maximal between 2 and 6 h and were more marked after clonidine than after tiamenidine. As tiamenidine 1.0 mg did not produce a hypotensive effect equivalent to clonidine 0.3 mg direct comparison of side-effects attributable to these agents proved difficult. The evidence suggests, however, that tiamenidine would cause sedation and reduction in salivary flow comparable to clonidine if given in an equivalent hypotensive dose.

Adult↗
PubMed1978

Urine cytology findings in analgesic nephropathy.

Urine cytology screening for neoplasm led to the detection of 3 urothelial carcinomas and 1 severe urothelial dysplasia in 98 patients with analgesic-induced papillary necrosis. A further 18 patients had changes suggesting that they were at risk of incurring malignancy in the near future. Routine urine cytology is recommended in all cases of analgesic nephropathy.

Analgesics↗
PubMed1978

Disopyramide serum and pharmacologic effect kinetics applied to the assessment of bioavailability.

1 Serum, urine and pharmacologic effect (prolongation of the QT interval) kinetics of the antiarrhythmic disopyramide have been investigated in eight volunteers after intravenous administration (2 mg/kg) and oral administration (300 mg) of the two commercially available preparations, Rythmodan (Roussel Laboratories) and Norpace (Searle Laboratories). 2 An open one compartment body model adequately described the kinetics of disopyramide in serum and urine. 3 After intravenous administration, the following average pharmacokinetic parameters were found: biological half-life, 7.8 h; total clearance, 95 ml/min; renal clearance, 54 ml/min; apparent volume of distribution, 60 litres. 4 After oral Rythmodan and Norpace, serum concentration profiles and urinary excretion data revealed significant differences in rates of absorption, times required to achieve peak serum concentrations and biological half-lives. These differences were largely due to the relatively slow absorption characteristics of Norpace. 5 The absence of hysteresis in plots of QT prolongation against disopyramide serum concentration after oral administration indicated that serum and pharmacologic effect kinetics were indistinguishable within a kinetically equivalent compartment. 6 Analysis of both serum and urine data showed that while Norpace had a significantly higher degree of bioavailability (P less than 0.005), the 5--15% difference between the two formulations should not normally be of any clinical significance.

Administration, Oral↗