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Biomedical subjects

B Combe

Publications and source records attributed to B Combe.

At least 37 records · Page 2Linked to original sources
PubMed2001

Bone mineral density of 704 amateur sportsmen involved in different physical activities.

The aim of the study was to analyze the relation between sports and bone mass. Seven hundred and four men with no history of chronic disease were questioned on their adolescent and adult sporting activities. Their total body (TB) and regional (head, spine, arms and legs) bone mineral density (BMD) were measured by dual-energy X-ray absorptiometry. BMD measurements and ratios of regional BMD to TB BMD were compared using a multiple regression analysis. Probands (mean age 30 years) were engaged in 14 sports activities: rugby, soccer, other team sports, endurance running, fighting sports, bodybuilding, multiple weightbearing activities, swimming, swimming with flippers, biking, rowing, climbing, triathlon and multiple mixed activities. They stated that they were practising a physical activity at the amateur level: 7.1 h/week between the ages of 11 and 18 years and 9 h/week between age 18 years and the day of the interview (no significant difference between physical activities). Rowers and swimmers had low TB BMD (1.22 and 1.17 g/cm2) and low leg BMD (1.37 and 1.31 g/cm2). Participants in rugby, soccer, other team sports and fighting sports had a high TB BMD (1.27-1.35 g/cm2) and high leg BMD (1.41-1.5 g/cm2). For head BMD, there was no stastistical difference among the different groups. Constructed ratios pointed out the site-specific adaptation of the skeleton: soccer player and runners had a higher leg ratio; bodybuilders, fighters, climbers and swimmers had a higher arm ratio; rugby players had a higher spine ratio. Head ratio was higher in non-weightbearing sports (rowing, swimming) than in weightbearing sports (rugby, team sports, soccer, fighting sports and bodybuilding). Thus the BMD and ratio differences among the 14 disciplines seem to be site-specific and related to the supposedly high and unusual strains created at certain sites during sport training by muscle stress and gravitational forces. Head ratio is closely related to the type of practice; its value could predict whether sport participants have developed the maximal peak bone mass they could achieve.

Absorptiometry, Photon↗
PubMed2001

Thalidomide: new indications?

Thalidomide, which was developed as a nonbarbiturate sedative agent, was taken off the market in 1961 after it was linked to a spate of major birth defects. Gradually, thalidomide was reintroduced for the treatment of a few skin diseases including leprous erythema nodosum, severe mucosal ulcers (e.g., associated with HIV infection or Behçet's disease), lymphocytic skin infiltrations, cutaneous lupus erythematosus, and chronic graft-versus-host disease. Recent reports of original pharmacological properties including modulation of cytokine production (mainly reduced TNF-alpha production) and inhibition of angiogenesis have led to the suggestion that thalidomide may be useful in some inflammatory and neoplastic conditions. Several open-label studies and case reports have described the effects of thalidomide in Crohn's disease, rheumatoid arthritis, ankylosing spondylarthritis, systemic sclerosis, and a few other systemic disorders. In these indications, minor but dose-limiting side effects were apparently common. Thalidomide analogs with better acceptability profiles are under evaluation. The anti-angiogenic effects of thalidomide may make this compound valuable as single-drug therapy or as an adjunct to chemotherapy in patients with cancer, particularly those with metastases or multiple myeloma. This possibility requires further evaluation.

Adjuvants, Immunologic↗
PubMed2001

HLA-DRB1 gene transcripts in rheumatoid arthritis.

Susceptibility to rheumatoid arthritis (RA) is associated with defined HLA-DRB1 alleles. However the molecular basis of this association is not known. Peculiarities in the expression of disease-linked DRB1 alleles could be involved since in healthy controls HLA-DRB1 gene expression varies according to the alleles in B cells. Peripheral blood B cells of healthy controls and RA patients were examined for their level of allelic DRB1 transcripts using a competitive PCR approach. Levels of DRB1 transcripts were greatly modified in RA and influenced by HLA-DRB1 genotype: patients with double dose of RA-associated alleles displayed up-regulated amounts of DRB1 gene transcripts whereas patients carrying either a single or no at risk allele had low levels of DRB1 transcripts, compared to control individuals. These differential levels of DRB1 gene expression were not influenced in any way by clinical, biological or therapeutic features of the patients. Various amounts of DRB1 mRNA may be related to variations of the density of DR molecules on B cells and consequently could influence the response of CD4 T cells. This particular regulation of DRB1 gene expression in RA patients could therefore represent one of the molecular mechanisms involved in the association of HLA DRB1 genes to RA.

Alleles↗
PubMed2001

HLA-DRB1 genes and patients with late onset rheumatoid arthritis.

OBJECTIVE: To determine the influence of HLA-DRB*1 genes on susceptibility to and severity of rheumatoid arthritis (RA) in patients with late onset compared with younger onset disease. METHODS: The clinical, biological, and HLA-DRB1 typing characteristics of two groups of patients were studied retrospectively. Group 1 consisted of 262 patients whose disease onset was before or at the age of 60 (young onset RA (YORA)). Group 2 included 60 patients whose illness began after the age of 60 (elderly onset RA (EORA)). RESULTS: The shared epitope level was similarly increased in both groups of patients compared with normal controls (195/262 (74%) in group 1 and 43/60 (72%) in group 2 v 645/1609 (40.1%) in controls). No differences were noted between the two groups of patients for each separate disease related allele. In contrast, when studying all HLA-DRB1*04 RA related alleles as a group, these alleles were underrepresented in EORA compared with YORA (22/60 (37%) v 135/262 (52%); odds ratio 2.0; 95% confidence interval 1.0 to 3.3). An inverse trend was seen for HLA-DRB1*01 alleles. There were no differences in biological characteristics or extra-articular manifestations between the patient groups. The differences noted in radiological evaluation or the number of prescribed disease modifying antirheumatic drugs seemed to be linked with differences in disease duration. CONCLUSION: HLA-DRB1 RA related alleles influence both EORA and YORA. However, HLA-DRB1*04 RA linked alleles are not as closely associated with RA in the elderly as they are in younger patients. This suggests that the importance of these genes in the susceptibility to RA may be lower in elderly patients.

Age of Onset↗
PubMed2001

Chondroitin sulfate in osteoarthritis of the knee: a prospective, double blind, placebo controlled multicenter clinical study.

OBJECTIVE: To assess the efficacy and safety of chondroitin sulfate (CS) 1 g/day per os compared to placebo, in a double blind, randomized, parallel group study, with 3 months treatment followed by a 3 month posttreatment period, in patients with femorotibial osteoarthritis (OA). METHODS: The main criterion was the functional handicap assessed by Lequesne's algofunctional index (AFI). Secondary efficacy criteria were: self-assessed pain with activity and at rest, self-assessed impact of OA on daily living, patient and physician assessed overall change in patient state since the previous visit, and daily NSAID and analgesic consumption, all evaluated monthly. The main analysis was performed on the intent-to-treat (ITT) population at treatment endpoint compared to baseline (Day 0). RESULTS: The ITT efficacy data set comprised 130 patients (63 in CS group and 67 in placebo group). At treatment endpoint, the AFI showed greater but nonsignificant improvement in the CS than in the placebo group. Improvement became significant (p = 0.02) in the completer population (n = 114). In the ITT population, all variables tended towards greater improvement in the CS than the placebo group. In the completer population, pain at rest also significantly decreased in the CS group compared to the placebo group (p = 0.03), and, one month after treatment, CS had a significantly higher persistent effect than placebo on the AFI (p = 0.01), pain with activity (p = 0.001), physician assessed patient state (p = 0.05), and most other efficacy criteria. Adverse event rates did not differ significantly. CONCLUSION: We observed a trend towards efficacy of CS 1 g/day compared to placebo with good tolerability after 3 month treatment, and persistent efficacy one month posttreatment. Further investigations are required to confirm this trend.

Administration, Oral↗
PubMed2001

[Factors predictive of severity in rheumatoid arthritis].

Rheumatoid arthritis (RA) is a very heterogeneous disease with multiple forms. Some are very mild with few or no overt lesions or joint deformations, others are very severe leading to rapid joint destruction and major functional handicap. The best therapeutic strategy for patients with early stage RA cannot be uniform, but must be adapted to each individual patient, depending on disease severity. This fact is becoming even more important with the development of new treatments which have had a major impact on therapeutic strategies. No prognostic factor has reached universal acceptance. There are however an increasing number of arguments allowing better recognition of prognosis during the early stages of the disease. High ESR, CRP, positive rheumatoid factor with a high IgM (and IgA) titer, the presence of one of the HLA DRB1*04 alleles associated with RA, and early development of radiological lesions are all factors of prognosis.

Alleles↗
PubMed2000

The down-regulation of HLA-DM gene expression in rheumatoid arthritis is not related to their promoter polymorphism.

HLA-DM molecule, a class II-like heterodimer, is a critical factor of HLA class II-dependent Ag presentation. It acts as a molecular chaperone and also functions as a peptide editor favoring the presentation of high-stability peptides. Thus, it appears to skew the peptide repertoire presented to T cells. Variation in HLA-DM expression has considerable effect on Ag presentation and regulation of these genes is likely to be a prerequisite to prevent autoimmunity. In this study, rheumatoid arthritis (RA) was chosen as a model of human autoimmune disease since its genetic susceptibility is known to be associated with the HLA-DR and -DM components. We described a limited nucleotide polymorphism in the HLA-DM promoters with functional impact on basal transcriptional activity and IFN-gamma induction as assessed in vitro. However, no difference of allele frequencies was found between controls and RA patients. Despite of this lack of association, expression of HLA-DM molecules was also investigated. Interestingly, an underexpression of HLA-DM transcripts and protein was shown in peripheral blood B cells from RA patients compared with controls or inflammatory arthritis patients. This underexpression does not affect HLA-DR genes and is responsible for a decrease of the DM:DR ratio in RA patients. This specific HLA-DM down-regulation is likely to have important consequences on Ag presentation and could participate in the autoimmune process in RA.

Arthritis, Rheumatoid↗
PubMed2000

Outcomes in patients with incipient undifferentiated arthritis.

OBJECTIVE: To determine outcomes in patients with onset within the last year of peripheral inflammatory arthritis that does not meet classification criteria for any specific disease. METHODS: Symptoms and laboratory tests were evaluated at baseline and 14 to 60 months later in 43 patients, 32 women and 11 men, with a mean age of 50 years. RESULTS: At baseline, a presumptive clinical diagnosis was made in 16 of the 43 patients. Diagnoses at last follow-up were undifferentiated inflammatory arthritis in seven cases, mild rheumatoid arthritis in 18, psoriatic arthritis in two, Sjögren's syndrome in two, lupus in one, and paraneoplastic syndrome in one. The remaining 12 patients were free of inflammatory joint symptoms; three had symptoms of osteoarthritis and nine were asymptomatic. Factors present at baseline and predictive of progression to definite rheumatoid arthritis were a positive test for rheumatoid factor, presence of an HLA DRB1*04 allele, and a presumptive clinical diagnosis of rheumatoid arthritis. CONCLUSION: 55% of our patients developed a specific inflammatory joint disease, and 42% developed rheumatoid arthritis, which was consistently mild. Resolution of all inflammatory joint symptoms occurred in 28% of cases. A number of clinical laboratory, and genetic findings of use for predicting the outcome of undifferentiated arthritis were identified.

Adult↗
PubMed2000

Folic acid alters methotrexate availability in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the effects of repeated doses of folic acid on the pharmacokinetics of methotrexate (MTX) in patients with rheumatoid arthritis. METHODS: We studied 20 patients (ages 30-78 years) who received MTX intramuscularly (10 mm/week). MTX was administered alone or after treatment with folic acid (5 mg tablet once daily) for 13 days. Plasma samples were collected 2 and 8 h after dose intake. MTX concentrations in plasma and ultrafiltrate samples were measured by fluorescence polarization immunoassay. A Bayesian approach was used to determine individual MTX pharmacokinetic variables to minimize the number of samples collected. RESULTS: Folic acid supplementation led to reduced plasma MTX levels 2 and 8 h after MTX administration and reduced area under the plasma MTX concentration versus time curve (AUC) (about 20%; p < 0.02). Total clearance of MTX and Vd were higher when patients were also receiving folic acid than when they were taking MTX alone (p < 0.02). The plasma protein binding of MTX remains unchanged. CONCLUSION: The lower plasma MTX concentrations in patients taking folic acid supplements could be interpreted as increased cellular uptake of MTX; the folic acid supplements would promote the sequestering of MTX intracellularly. The decrease of MTX concentrations leads to reduced AUC; it is also possible that there are reduced AUC combined with increased intracellular folate levels. These results reopen the question of whether folic acid should be used immediately in all patients when MTX is begun.

Adult↗
PubMed1999

Intracytoplasmic Th1 and Th2 cytokines in rheumatoid arthritis blood and synovial tissue.

In rheumatoid arthritis (RA), T cells have been proposed either as a main actor or as an epiphenomenon in such a primarily synoviocyte-driven disease. A major issue remains the remarkable paradox between the T cell infiltrate and the relative failure to detect definite markers of their activity. To determine the Th1/Th2 cytokine profile in RA synovium, we used a single cell flow cytometric assay for interleukin-2 (IL-2), interferon-gamma (IFN-gamma), IL-4 and IL-10 in paired peripheral blood (PB) and synovial tissue (ST) lymphocytes from RA and osteoarthritis (OA) patients and PB lymphocytes from healthy controls. Cytokines were undetectable in unstimulated PB and ST lymphocytes. More stimulated PB and ST CD4(+)lymphocytes produced IFN-gamma than IL-4, for all individuals tested. RA PB CD4(+)lymphocytes showed the same Th1 cytokine pattern as normal controls. No increase of such a Th1 profile was observed for ST lymphocytes. A specific recruitment of T CD4(+)lymphocytes in the rheumatoid inflamed synovium could not be concluded on the basis of these results.

Adult↗
PubMed1999

Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components.

OBJECTIVES: To investigate the potential clinical benefit of a combination therapy. METHODS: 205 patients fulfilling the ACR criteria for rheumatoid arthritis (RA), not treated with disease modifying antirheumatoid drugs previously, with an early (< or = 1 year duration), active (Disease Activity Score (DAS) > 3.0), rheumatoid factor and/or HLA DR 1/4 positive disease were randomised between sulphasalazine (SASP) 2000 (maximum 3000) mg daily (n = 68), or methotrexate (MTX) 7.5 (maximum 15) mg weekly (n = 69) or the combination (SASP + MTX) of both (n = 68). RESULTS: The mean changes in the DAS during the one year follow up of the study was -1.15, -0.87, -1.26 in the SASP, MTX, and SASP + MTX group respectively (p = 0.019). However, there was no statistically significant difference in terms of either EULAR good responders 34%, 38%, 38% or ACR criteria responders 59%, 59%, 65% in the SASP, MTX, and SASP + MTX group respectively. Radiological progression evaluated by the modified Sharp score was very modest in the three groups: mean changes in erosion score: +2.4, +2.4, +1.9, in narrowing score: +2.3, +2.1, +1.6 and in total damage score: +4.6, +4.5, +3.5, in the SASP, MTX, and SASP + MTX groups respectively. Adverse events occurred more frequently in the SASP + MTX group 91% versus 75% in the SASP and MTX group (p = 0.025). Nausea was the most frequent side effect: 32%, 23%, 49% in the SASP, MTX, and SASP + MTX groups respectively (p = 0.007). CONCLUSION: This study suggests that an early initiation therapy of disease modifying drug seems to be of benefit. However, this study was unable to demonstrate a clinically relevant superiority of the combination therapy although several outcomes were in favour of this observation. The tolerability of the three treatment modalities seems acceptable.

Antirheumatic Agents↗
PubMed1999

Anti-heat shock protein 70 kDa and 90 kDa antibodies in serum of patients with rheumatoid arthritis.

OBJECTIVES: Stress proteins (HSPs) are highly conserved immunodominant antigens found in various species. The purpose of this study was to assess the prevalence and prognostic significance of antibodies to HSC 70 kDa and HSP 90 kDa in three groups of patients with longstanding rheumatoid arthritis (RA) defined based on the severity of articular erosions. METHODS: 73 patients with longstanding (> 6 years) RA whose HLA-DR genotype was known were divided in three groups according to Larsen's score and compared with 47 recent onset (<1 year) RA patients and with control groups composed of patients with other inflammatory diseases (n=137) or of normal controls (n=48). IgGs and IgMs to HSC 70 kDa and HSP 90 kDa were determined using an ELISA with purified bovine HSC 70kDa or HSP 90 kDa. RESULTS: Concentrations of IgGs and IgMs to HSC 70 were significantly increased in 41.1% and 42.5% of longstanding RA patients, respectively. Corresponding figures for IgGs and IgMs to HSP 90 were 39.7% and 56%. IgMs to HSC 70 and HSP 90 were less frequent in recent onset RA (19% and 13% respectively). Among the groups with other inflammatory diseases, only the MCTD group exhibited high frequencies of IgGs to HSC 70 (80%) and HSP 90 (85%). DRB1*0401 positive RA patients (n=23) were not more likely to have increased concentrations of antibodies to HSC 70 kDa or HSP 90 kDa than other RA patients (DR4 positive but DRB1*0401 negative, or DR1 positive, n=31; or negative for both DR4 and DR1, n=14). IgGs to HSP 90 kDa were significantly more frequent (p<0.05) in longstanding RA patients whose Larsen's score was 4 or more (57%) than in those whose Larsen's score was 2 or 3 (39.4%) or less than 2 (16%). No associations were found between Larsen's score and IgGs or IgMs to HSC 70 kDa or IgMs to HSP 90 kDa. A significant correlation was demonstrated between IgGs to HSP 90 kDa and two other serological markers for RA, rheumatoid factor, and anti-Sa antibody; there were no correlations with antikeratin antibody, antiperinuclear factor, or anti-RA 33. CONCLUSION: IgGs to HSP 90 kDa are most common in longstanding RA patients with articular erosions, suggesting that they may be related to the articular prognosis in RA

Adolescent↗
PubMed1999

Anti-Sa antibody is an accurate diagnostic and prognostic marker in adult rheumatoid arthritis.

OBJECTIVES: To evaluate in various groups of patients with chronic joint disease the sensitivity and specificity of anti-Sa antibody, recently described in sera from adults with rheumatoid arthritis (RA); and to determine the prognostic significance of anti-Sa in initial sera from patients with long standing RA with or without severe joint destruction. METHODS: Serum samples from 489 patients were included. Of these, 154 were collected from patients with RA attending 2 rheumatology units. Controls were 335 patients with a variety of inflammatory joint diseases other than RA. IgG anti-Sa was detected using an immunoblotting method with purified Sa antigen from human placenta extracts. All patients were tested for the following antibodies: rheumatoid factor (RF), anti-keratin antibody (AKA), antiperinuclear factor (APF), and anti-RA 33. HLA class II DRB alleles were also determined. RESULTS: Anti-Sa was detected in 39.8% of RA sera overall, 46.7% of sera from the long standing RA group, and 23.5% of sera from the recent onset RA group (p<0.01). In patients with long standing RA, statistically significant associations were found between the presence of anti-Sa and the following variables: RF (p<0.0001), AKA (p<0.0001), APF (p<0.00001), and HLA DRB1*04 or 01 (p<0.01). In contrast, no association was found with anti-RA33. Anti-Sa was positive in 11 adult controls (7.8%) and in 26 pediatric patients with juvenile chronic arthritis (22%). The specificity of anti-Sa for RA was 92.1% in adults with well characterized rheumatic diseases and 85.9% in adults and children together. Among patients with long standing RA, those with destructive disease were more likely to test positive for anti-Sa (66.6%) than those with nondestructive disease (22.2%) (p<0.0001). Comparisons with other serologic markers for RA demonstrated that anti-Sa was sensitive (68.4%) and was also the test with the highest specificity (79%), positive predictive value (75%), and negative predictive value (71%) for discriminating between patients who do and those that do not develop late severe radiographic damage. CONCLUSION: Immunoblot-detected IgG anti-Sa is a sensitive serologic marker for RA patients with severe radiographic damage.

Adult↗
PubMed1999

Radiologic progression in early rheumatoid arthritis treated with methotrexate.

OBJECTIVE: To evaluate radiologic progression in patients with early rheumatoid arthritis (RA) receiving methotrexate (MTX) as the first slow acting drug. METHODS: An open, prospective study of 29 patients with RA (21 F, 8 M, mean age 48.5+/-15.4 yrs). The mean duration of RA was 6.6 (2-60) months; and rheumatoid factor was present in 11 cases. Clinical, biological, and radiographic evaluations were done before the start of MTX treatment and after 13+/-3.8 months. Radiographs of hands and wrists were blindly studied by 2 physicians, using Larsen's and modified Sharp's methods. There was a significant correlation for the scores of the 2 physicians evaluated by kappa coefficient. Radiographic evolution was defined as an increase of 15 points in the radiologic score by each method used. RESULTS: Patients showed significant clinical improvement after one year of MTX treatment. Despite clinical and biological improvement, significant mean radiographic progression was noted, with Larsen's method (p = 0.001) and Sharp's method (p = 0.034), without reaching the maximum score. However, using the definition of radiographic progression, the radiologic scores indicated stabilization in 23 patients with Larsen's method and in 24 patients with Sharp's method. CONCLUSION: This study revealed mild radiographic progression in early RA patients treated with MTX for one year. Further controlled studies are needed.

Antirheumatic Agents↗
PubMed1998

[Rheumatoid polyarthritis: therapeutic management].

AN OPEN QUESTION: Developing a therapeutic strategy for rheumatoid arthritis is a difficult and much debated task. Recent clinical trials have confirmed the importance of initiating treatment at the onset of disease in all patients with rheumatoid arthritis in order to limit the degree of later progression. INDIVIDUALIZED REGIMENS: Treatment for patients with early-stage rheumatoid arthritis should be adapted individually taking into consideration the expected benefit and risks of drug therapy, the degree of joint inflammation and factors predictive of disease severity which are becoming more and more well understood. PATIENTS IN REMISSION: Treatment should be continued if well tolerated. Treatment should not be discontinued (and then only progressively) unless complete remission has been achieved for a long period. LONG-STANDING DISEASE: The precise therapeutic strategy in patients with long-standing disease remains a question of debate, but does require full-dose combination regimens.

Anti-Inflammatory Agents↗
PubMed1998

[Inflammation and joint destruction during rheumatoid polyarthritis: what relation?].

UNLABELLED: A QUESTION REVISITED: It is generally accepted that acute then chronic joint inflammation leads to the development of a synovial pannus and secondarily to characteristic degenerative joint disease en rheumatoid arthritis. However accumulating clinical and biological evidence would question the real relationship between inflammation and joint destruction, and suggest therapeutic strategies might need to be revisited. THE CAUSAL EVENTS: Synovial proliferation is the fundamental event in joint lesions. The contact between the synovial pannus and the cartilage leads to characteristic joint damage mediated by pro-inflammatory cytokines (TNF alpha and IL 1) and enzyme secretion, particularly metalloproteases. ROLE OF T CELLS: The role of T-lymphocytes is a question of much debate. Although it is generally accepted that T cells are crucial in the initial phases of rheumatoid arthritis, several arguments suggest that the process of synovial proliferation and joint destruction in advanced stage disease would be independent of T cell activity. Synovial macrophages and fibroblasts, and perhaps chondrocytes, play a central role at this phase. THERAPEUTIC IMPLICATIONS: A direct mandatory relationship between inflammation and joint destruction appears to be excluded, although complex and poorly understood links exist between these events in rheumatoid arthritis. A better understanding of the mechanisms involved would be very useful for the development of more adapted therapeutic strategies in rheumatoid arthritis.

Arthritis↗
PubMed1998

Effects of moderate renal insufficiency on pharmacokinetics of methotrexate in rheumatoid arthritis patients.

OBJECTIVES: To determine the effects of impaired renal function on the pharmacokinetics of methotrexate (MTX) in rheumatoid arthritis (RA) patients. METHODS: 77 RA patients were included in this study. MTX was administered intramuscularly (7.5 to 15 mg). Subjects were divided into four groups, according to their creatinine clearance (CLCR); group 1: CLCR lower than 45 ml/min; group 2: CLCR between 45 and 60 ml/min, group 3: CLCR between 61 and 80 ml/min and group 4: CLCR higher than 80 ml/min. Blood samples were collected from each subject before drug administration and at two and eight hours after administration. Individual pharmacokinetic parameters were estimated using a Bayesian approach. RESULTS: MTX concentrations (total and free) were 1.3 to 1.6-times higher in group 1 than in groups 2, 3, and 4. For total and free MTX, t1/2 eliminations were 22.7 hours in group 1, 13.5 hours in group 2, 12 hours in group 3, and 11 hours in group 4. Clearance of total MTX was 64, 92, 96, 115 ml/min in groups 1 to 4, respectively, it was 118, 163, 171, 206 ml/min in groups 1 to 4 for the free MTX, respectively. Volume of distribution averaged 2.16 l/kg in group 1, 1.92 l/kg in group 2, 1.61 l/kg in group 3, and 1.56 l/kg in group 4. Elimination half life was significantly increased and total clearance was significantly reduced with the degree of renal impairment. Linear regression revealed good correlations between clearance values of MTX and creatinine clearance. CONCLUSION: Individual testing is required rather than a general decrease of the MTX dose based only on CLCR.

Aged↗