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Biomedical subjects

N Christophidis

Publications and source records attributed to N Christophidis.

52 records · Page 3Linked to original sources
PubMed1982

Intra-articular drug therapy in rheumatoid arthritis. A study with indoprofen.

Six patients (4 men, 2 women) with moderate/large knee effusions due to rheumatoid arthritis (RA) were studied after receiving indoprofen, 25 mg intra-articularly and then 200 mg orally 1 week later. There was significant improvement in pain (t = 3.74, P less than 0.05), morning stiffness (t = 2.91, P less than 0.05) and range of movement (t = 2.52, P less than 0.05) for at least 1 week following the intra-articular injection. The terminal phase plasma half-life after the 200 mg oral dose was 6.4 +/- 0.7 h (mean +/- SEM) and was significantly longer than the often quoted plasma half-life of 2-3 h from previous studies, but much less than the pharmacodynamic half-life. Synovial fluid concentration were not significantly different from those in plasma in the post-distribution phase. Intra-articular indoprofen may be a useful addition to the treatment of RA.

Administration, Oral↗
PubMed1981

Renal clearance of methotrexate in man during high-dose oral and intravenous infusion therapy.

The renal excretion and clearance of methotrexate (MTX) following high-dose (800 mg) therapy followed by folinic acid rescue was studied in 12 patients (2 female, 10 male): the mean age was 49.3 +/- 5.5 (SE), weight 68.6 +/- 3.9 (SE) and body surface area 1.8 +/- 0.1 m2. Plasma and urine were collected over 154 h at intervals of 2-24 h, and the collection times, volume, and pH of urine samples recorded. Total MTX concentrations in urine and plasma were measured by the highly specific competitive protein-binding assay method. Plasma and urinary creatinine levels were measured on an SMA-12 autoanalyser. The renal clearance of MTX was calculated for each urine collection period. Following oral administration, clearance values during the first 6 h were high at 257 +/- 8.3 (ml/Min), followed by a trough in clearance of 27.9 +/- 4.2 (ml/min) in the 20- to 30-h period. This was followed by a secondary rise of MTX renal clearance to 180.4 +/- 14.6 ml/min during the 68- to 84-h period and again to 84.9 +/- 17.1 ml/min between 84 and 112 h. In the last two periods it rose to 209 +/- 57.9 ml/min. Similar fluctuations were seen following IV administration. The changes in clearance were statistically significant at the p less than 0.005 level. It is suggested that high concentrations of MTX in the renal tubules result in inhibition of carrier protein synthesis, leading to a fall in active tubular secretion. When MTX concentrations fall the tubular cell recovers and a secondary rise in renal clearance occurs, leading to cyclical changes in MTX elimination.

Administration, Oral↗
PubMed1981

How frequently should anti-inflammatory drugs be given? A study with indoprofen.

Indoprofen, despite its relatively short plasma half-life, was just as effective given twice daily as when the same daily total was given in four divided doses. There was a trend in favour of the twice daily regime for changes in morning pain and the duration of morning stiffness. Preferences were equally divided between the two regimes and efficacy was the usual reason for patients preferring one or other. Side-effects were no more frequent with the twice daily regime. Pharmacokinetics are no substitute for clinical experiment in planning the dosage regime of a non-steroidal anti-inflammatory drug.

Arthritis, Rheumatoid↗
PubMed1980

Hypertensive responses induced by phenylpropanolamine in anorectic and decongestant preparations.

The acute effects of a single capsule of each of two phenylpropanolamine-containing preparations were determined in a group of healthy young adults, by means of a double-blind comparison with matching placebo preparations. Supine diastolic blood-pressure rose to 100 mm Hg or more in 12 out of 37 subjects taking an anorectic preparation ('Trimolets'; 85 mg phenylpropanolamine per capsule) and in 4 out of 34 subjects taking a decongestant preparation ('Contac 500'; 50 mg phenylpropanolamine per capsule). 20 of the subjects taking trimolets reported adverse side effects. The frequency and extent of the hypertensive response to high-dose phenylpropranolamine-containing preparations suggest that clinical use of such preparations should be reviewed and that their availability without prescription may not be appropriate.

Adult↗
PubMed1979

Comparison of intravenous and oral high-dose methotrexate in treatment of solid tumours.

An outpatient regimen of oral high-dose methotrexate was studied in 14 patients with solid tumours over 12 months. Detailed pharmacokinetic analysis in five patients showed high oral bioavailability (mean +/- SE of mean 87.6 +/- 1.5%), indicating that with this regimen oral methotrexate was well absorbed and the first-pass effect low. Oral administration resulted in peak plasma methotrexate concentrations of 8.4 +/- 0.5 mumol/l (382 +/- 23 microgram/100 ml) and was almost as effective as intravenous administration, which achieved peak concentrations of 9.9 +/- 0.4 mumol/l (450 +/- 18 microgram/100 ml). In all 14 patients the clinical response to oral treatment was comparable to that reported to intravenous administration of high-dose methotrexate used in combination with other cytotoxic drugs. The disease-free interval in cases of adult sarcoma was 7.4 +/- 1.3 months and the relapse rate 29%. Out of four patients with small-cell carcinoma, two showed an objective response to oral treatment. We suggest that oral high-dose methotrexate given in divided doses is a rational alternative to expensive intravenous high-dose methotrexate regimens, but further clinical evaluation is necessary.

Administration, Oral↗
PubMed1979

Ocular side effects with 5-fluorouracil.

The concentrations of 5-fluorouracil in tears and plasma were studied in eight patients receiving the drug for carcinoma of the colon. The drug was measured by a gas liquid chromatographic method and found to be present only in the tears of patients with excessive lacrimation. In three patients with watery eyes the peak concentration in tears (16-23.8 micrograms/ml) occurred 15 minutes after IV administration and this corresponded with the end of the distribution (alpha) phase in the plasma when the plasma levels ranged from 18-26 micrograms/ml. In five patients without eye symptoms the drug was undetectable in the lacrimal fluid even though they had similar plasma levels (15-25 micrograms/ml) of 5-fluorouracil. The volumes of distribution and plasma clearance rates were similar in the two groups [being 0.2-0.52 (mean = 0.33) 1/kg and 612-978 (mean = 850) ml/min respectively in patients with excessive lacrimation and 0.13-0.79 (mean = 0.36) 1/kg and 435-1138 (mean = 831) ml/min respectively in the five patients without symptoms.]. It appears that 5-fluorouracil produces irritation of the lacrimal apparatus in about 30% of patients on the drug and in association with this appears in the tears where it may be responsible for the reported irritation and fibrosis of the tear duct.

Chromatography, Gas↗
PubMed1979

Comparison of liquid- and gas-liquid chromatographic assays of 5-fluorouracil in plasma.

A liquid-chromatographic assay of 5-fluorouracil in plasma is described. Advantages of this procedure over gas chromatography are the simpler extraction procedure, elimination of the need for a derivitization step with silylating agents, and a 20-fold greater sensitivity. The minimum detectable concentration of 5-fluorouracil in plasma is 25 microgram/L. The enhanced sensitivity enabled measurement of the concentrations of 5-fluorouracil found in plasms of patients receiving continuous intravenous infusions of the drug; such concentrations are generally unmeasurable by gas-chromatographic methods. We compared liquid-chromatographic and gas-chromatographic measurements on 36 plasma samples obtained from patients after rapid intravenous injection of 5-fluorouracil. The resulting correlation coefficient was 0.97, with a regression slope of 0.94. The liquid-chromatographic method is free of interference from other cytotoxic agents, anti-emetics, and folate derivatives that are frequently combined with 5-fluorouracil therapy.

Chromatography, Gas↗
PubMed1978

Studies of intravenous cefoxitin (MK306).

The pharmacokinetics of cefoxitin, a new cephamycin antibiotic, were studied in six patients who were undergoing total hip replacement, and who were given cefoxitin to provide prophylactic cover at the time of operation. Later, the efficacy of cefoxitin was studied in nine patients with severe acute infections. The mean elimination phase half-life of cefoxitin which was obtained in this study (83 to 87 minutes) was significantly longer than that obtained in other studies. Cefoxitin was also found to be effective in lung and urinary tract infections against sensitive organisms. It was well tolerated, and the only side effect was that of phlebitis in long-term therapy. Cefoxitin may be valuable for prophylactic use in bowel and orthopaedic surgery.

Aged↗
PubMedDate not supplied

Verapamil in the treatment of hypertension.

A randomized, double-blind, crossover trial was carried out in 17 hypertensive patients to evaluate the hypotensive efficacy and safety of verapamil. Verapamil in doses of 120 mg thrice daily was compared with pindolol in doses of 7.5 mg twice daily. A thiazide diuretic was given with both drugs. Blood pressure fell about 14/11 mm Hg during treatment with either drug compared to the placebo period, and neither drug caused significant side effects. Verapamil did not affect plasma renin concentration.

Adult↗
PubMedDate not supplied

Methotrexate polyglutamate levels in circulating erythrocytes and polymorphs correlate with clinical efficacy in rheumatoid arthritis.

OBJECTIVES: To measure MTX polyglutamates in circulating erythrocytes (E-MTX), mononuclear cells (MNC-MTX) and polymorphs (PMN-MTX) in rheumatoid arthritis (RA) patients and to see whether these correlated with clinical efficacy and side effects. METHODS: Sixty-five patients (40F, 25M; mean age 57 yrs.) with RA (ARA revised criteria) who had been on weekly pulse MTX (2.5-37.5 mg) for at least 2 months were entered into this study. The patients were classified as responders (R), partial responders (PR) or non-responders (NR) when blood was sampled for the MTX determination. Side effects since the initiation of MTX were also recorded. MTX-polyglutamates were measured (blinded to clinical details) using an enzymatic assay. RESULTS: E-MTX in responders and partial responders were significantly higher (p < 0.001) than in non-responders. Similarly, PMN-MTX were also higher, but the difference was only significant for the R group (p = 0.0019). The differences in concentrations could not be explained on the basis of the dose, which tended to be higher in NR than in R (p = 0.085). The concommitant prednisolone dose was significantly lower in R than in NR (p = 0.001), as were the ESR and CRP (p = 0.007, and p = 0.05 respectively), but the MCV was higher (p = 0.047). E-MTX tended to be higher in patients with side effects, but this difference did not reach statistical significance (p = 0.15). CONCLUSION: The results suggest that circulating intracellular levels of MTX polyglutamates in RBC and PMN correlate with clinical efficacy but not with toxicity in patients with RA.

Adult↗
PubMedDate not supplied

Modulation of the iodination reaction in normal human neutrophils and in whole blood by penicillamine, congeners and intracellular enzyme catalase and superoxide dismutase.

We have demonstrated that penicillamine (PSH) has the capacity to effect phagocytic cells by its interaction with the myeloperoxidase-halide system (MPOHS). We have undertaken studies at the cellular level, measuring the activity of the MPOHS through quantitation of I125 uptake (free and bound), known as the iodination reaction (i.e., in isolated polymorphonuclear leukocytes (PMN) and in whole blood). In contrast to other studies investigating the effects of PSH on isolated myeloperoxidase (MPO), we have shown that PSH scavenges the H2O2 produced by phagocytic cells, thereby reducing the availability of H2O2 for conversion to HOI125 by myeloperoxidase. This was observed as a reduction in the level of iodination. This finding is supported by our having obtained similar results in PMN and whole blood with catalase (C), glutathione (GSH) and N-acetylcysteine (NAC) but not with penicillamine disulphide (PSSP) or superoxide dismutase. Cu2+ (8 microM) when incubated with PSH reduced the level of inhibition of the iodination reaction by the oxidation of PSH to PSSP, illustrating the importance of the free sulphydryl group for this action. Incubation of PMN or whole blood for 0 to 2 hours with PSH, with a subsequent washing of PMN prior to stimulation, showed that PSH (free) requires to be present during stimulation of phagocytic cells to have this effect on the iodination reaction. Superoxide dismutase (SOD) produced increases in the iodination reaction in stimulated PMN by increasing the availability of H2O2. In conclusion, PSH inhibits the myeloperoxidase-halide system at a cellular level by scavenging H2O2 rather than by oxidation of the myeloperoxidase enzyme. This was observed at clinically relevant concentrations of PSH.

Catalase↗
PubMedDate not supplied

Effects of non-steroidal anti-inflammatory drugs (NSAIDs) on human polymorphonuclear leucocyte function in buffer and plasma.

OBJECTIVE: To elucidate the mechanism of action of a wide range of non-steroidal anti-inflammatory drugs (NSAIDs) on the respiratory burst of isolated normal PMNs in buffered saline and plasma. METHODS: The oxidative burst of PMN was assessed by luminol enhanced chemiluminescence and myeloperoxidase-mediated iodination. Cells were stimulated by the synthetic tripeptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), serum coated zymosan or the phorbol ester phorbol myristate acetate (PMA). RESULTS: When using buffered saline as the suspending medium, tenoxicam, piroxicam, ibuprofen, ketoprofen and diclofenac, at concentrations achieved clinically, inhibited both PMA- and FMLP-induced luminol chemiluminescence. Tenoxicam and piroxicam in buffered saline also inhibited the iodination reaction. However, in plasma, which mimics the in vivo situation more closely, the inhibitory effect was markedly reduced. Only tenoxicam and piroxicam were found to cause the inhibition of luminol chemiluminescence at concentrations achieved clinically. CONCLUSION: If these study conditions are representative of the in vivo pathological state, the results suggest that only tenoxicam, piroxicam and possibly diclofenac sodium are likely to possess anti-inflammatory properties which are independent from effects on cyclooxygenase.

Anti-Inflammatory Agents, Non-Steroidal↗