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Biomedical subjects

M McLaren

Publications and source records attributed to M McLaren.

At least 19 recordsLinked to original sources
PubMed1995

Effect of nifedipine on changes in fibrinogen and von Willebrand factor in haemodialysis patients treated with recombinant human erythropoietin.

Erythropoietin (EPO) therapy in haemodialysis patients may be associated with the development of hypertension and vascular access thrombosis. Raised levels of fibrinogen and von Willebrand factor have been implicated in the pathophysiology of thrombosis under these circumstances. The effect of nifedipine, used to treat EPO therapy-related hypertension, on levels of fibrinogen and von Willebrand factor antigen (vWf) was studied in a group of 21 EPO-treated haemodialysis patients. Significant increments in both fibrinogen and vWf following EPO therapy were observed in the 13 patients who did not receive nifedipine (fibrinogen (median range), pre-EPO: 3.73 (2.41-6.38) mg/ml, post-EPO: 4.59 (3.03-8.80) mg/ml, P < 0.05; vWf pre-EPO: 183 (118-374)% normal, post-EPO: 253 (124-392)% normal, P < 0.01). Similar changes were not seen in the eight nifedipine-treated patients (fibrinogen, pre-EPO: 3.35 (2.58-6.32) mg/ml, post-EPO: 3.36 (2.69-7.20) mg/ml, P = NS; vWf, pre-EPO: 176 (104-298)% normal, post-EPO: 175 (82-371)% normal, P = NS). These effects were independent of blood pressure control. The use of nifedipine to treat EPO therapy-related hypertension may therefore potentially help to reduce the risk of vascular access thrombosis.

Erythropoietin↗
PubMed1995

A comparative study of captopril and enalapril on endothelial cell function in congestive heart failure patients.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce the incidence of future coronary artery thromboses in postmyocardial infarction patients. A possible prothrombotic role for the angiotensin system has been postulated, and support for this has been provided by a recent study that demonstrated that an infusion of angiotensin increases levels of the prothrombotic plasminogen activator inhibitor (PAI). In the current study the authors have investigated the effect of two ACE inhibitors, captopril and enalapril, on tissue plasminogen activator (tPA) and PAI in 33 congestive heart failure (CHF) patients. Blood samples were obtained pretreatment and then at weeks 1, 12, and 24 after initiation of ACE inhibitor therapy for measurement of tPA antigen and PAI activity levels. The results of the study indicated that the initiation of ACE inhibitors had no significant effects on tPA antigen or PAI activity levels at the time points studied, and no significant differences were demonstrated between captopril and enalapril. The results suggest, therefore, that ACE inhibitors do not affect tPA antigen or PAI activity in CHF patients, and thus another mechanism is probably responsible for the observed decrease in coronary artery thromboses in post-MI patients treated with ACE inhibitors.

Aged↗
PubMed1993

Effect of erythropoietin therapy and withdrawal on blood coagulation and fibrinolysis in hemodialysis patients.

Erythropoietin (EPO) therapy in hemodialysis patients may be associated with an enhanced risk of vascular access and extracorporeal thrombosis. Assessment of blood coagulation and fibrinolysis was performed monthly on a group of 21 hemodialysis patients treated with EPO, and on four iron-deficient hemodialysis patients treated with iron dextran infusions alone. Seventeen of the EPO treated patients were also monitored after withdrawal of EPO to allow hemoglobin to fall to pre-EPO levels, and 16 of these patients during a second subsequent phase of EPO therapy with EPO administered using the alternative route (subcutaneous/intravenous) from the first phase of treatment. Ten untreated hemodialysis patients with intrinsically high hemoglobins were studied as controls. EPO was associated with significant increases in the endothelial product Factor VIII von Willebrand factor antigen (FVIIIvWFAg), and plasma fibrinogen, to levels comparable to those observed in the untreated control patients. Both FVIIIvWFAg and fibrinogen remained significantly elevated when EPO was withdrawn. Whole blood platelet aggregation (spontaneous, collagen, and ADP-induced) also increased following EPO, collagen and ADP-induced aggregation, increasing further when EPO was withdrawn. Transient but significant changes occurred in plasma measures of thrombin-antithrombin III complex, prostacyclin stimulating factor, and protein C during the first EPO treatment phase, and also thrombin-antithrombin III complex during the second treatment phase, all favoring a tendency to thrombosis. D-dimer increased significantly following EPO withdrawal. Erythrocyte deformability, and granulocyte aggregation did not change. There was no effect of route of EPO administration (subcutaneous or intravenous) or EPO dose on any of these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Cicaprost, an orally active prostacyclin analogue: its effects on platelet aggregation and skin blood flow in normal volunteers.

1. Prostacyclin (PGI2) and its analogues may be useful in peripheral vascular disease. However, most have to be given intravenously due to their metabolic instability. 2. We have investigated the pharmacological effects of cicaprost, a synthetic PGI2 analogue which is metabolically stable and bioavailable after oral administration, in eight healthy male volunteers. 3. This was a double-blind, placebo-controlled, cross-over study. The volunteers were given either placebo, 5 micrograms, 7.5 micrograms or 10 micrograms cicaprost (at 09.00 h, 14.00 h, 19.00 h and again at 09.00 h the following day) on four separate occasions each 14 days apart. 4. Platelet aggregation induced by collagen and ADP in platelet rich plasma (PRP) and whole blood were measured prior to and 1 h after the trial medication. Laser Doppler flowmetry measured skin blood flow on the face before and after medication. 5. There was a statistically significant dose relationship in the inhibition of platelet aggregation induced by 2 microM ADP and 0.4 microgram ml-1 collagen in PRP and 2 microM ADP and 0.6 microgram ml-1 collagen in whole blood by cicaprost (P = 0.008, P = 0.34, P = 0.011 and P = 0.036, respectively). The threshold dose was 7.5 micrograms. Attenuation of anti-platelet effects was seen with the 14.00 h and 19.00 h doses. This may be due to a decrease in absorption after meals or to the development of tachyphylaxis. 6. Similar dose dependent effects of cicaprost on skin blood flow were also found (P = 0.01 and P = 0.006 for maximum output signal and red blood cell flux, respectively). The threshold dose was 7.5 micrograms. 7. In conclusion, cicaprost has significant anti-platelet and vasodilatory effects when given in doses of 7.5 micrograms and 10 micrograms three times a day in healthy male volunteers.

Adult↗
PubMed1993

Baseline plasma fibrinolysis and its correlation with clinical manifestations in patients with Raynaud's phenomenon.

OBJECTIVES: (1) To assess if patients with various forms of Raynaud's phenomenon (RP) have abnormal plasma fibrinolysis that may contribute to diminished digital blood flow; (2) to assess whether patients with RP with evidence of endothelial damage have abnormal plasma fibrinolysis; (3) to determine the clinical relevance of abnormalities, if any, in plasma fibrinolysis in patients with RP. METHODS: One hundred and sixty eight patients with significant RP were studied--46 had primary Raynaud's disease (RD), 32 had suspected Raynaud's syndrome secondary to an undifferentiated connective tissue disorder (undifferentiated CTD), 25 had Raynaud's syndrome associated with atherosclerosis (athero RS), and 65 had an underlying connective tissue disease (CTD RS). All attended in the morning after a low fat light breakfast. After a clinical history was obtained, venous blood samples were collected without stasis for assays of plasma fibrinolysis and factor VIII von Willebrand factor antigen (fVIII vWF Ag). Results were compared with those obtained from normal subjects matched for sex and age. As patients with athero RS were significantly older than the other patients with Raynaud's phenomenon, two groups of control subjects were recruited--namely, 'old' and 'young' control subjects. RESULTS: Patients with CTD RS and athero RS had higher concentrations of fVIII vWF Ag (CTD RS median 174.5 range (45-370)% v 100 (38-202)%, p < 0.001; athero RS 182-5 (100-240)% v 100 (50-158)%, p < 0.001). Both had raised fibrinogen (CTD RS 3.25 (1.9-6.8) g/l v 2.4 (1.2-4.2) g/l, p < 0.001; athero RS 3.4 (2.2-6.2) g/l v 2.5 (1.8-3.9) g/l, p < 0.001) and both had diminished fibrinolysis with reduced plasminogen activator activity (CTD RS 79.5 (31-72) mm2 v 92 (37-197) mm2, p < 0.04; athero RS 73 (45-125) mm2 v 98 (41-197) mm2, p < 0.03). Patients with CTD RS also had raised plasminogen activity (3.3 (2.3-5.8) cU/ml v 2.9 (1.5-5.4) cU/ml, p < 0.001). On the contrary, patients with primary RD and undifferentiated CTD had normal fibrinogen and plasma fibrinolysis. Within each patient group, no significant differences in any of the measured variables were found between those who had RP all year and those who had RP in the winter only, those with RP of the hands only and of hands and feet, or those with and without digital ulcers. CONCLUSION: Diminished plasma fibrinolysis is found in patients likely to have endothelial damage (CTD RS and athero RS). These changes are probably a consequence rather than a cause of the disease.

Arteriosclerosis↗
PubMed1993

Abnormal plasma fibrinolysis in patients with rheumatoid arthritis and impaired endothelial fibrinolytic response in those complicated by vasculitis.

OBJECTIVES: (a) To assess plasma fibrinolytic parameters in patients with rheumatoid arthritis (RA) and to determine whether there are differences between patients with RA alone and those with RA complicated by vasculitis. (b) To determine if patients with RA respond differently to venous occlusion compared with normal subjects and to assess whether such a response differs in patients with RA alone and those with rheumatoid vasculitis. (c) To determine the extent of vascular damage in patients with rheumatoid vasculitis and if this correlates with the levels of plasma fibrinolytic parameters. METHODS: Sixty three patients with RA (38 had RA only and 25 had evidence of rheumatoid vasculitis) were recruited. Plasma levels of tissue plasminogen activator antigen (t-PA Ag), plasminogen activator inhibitor (PAI) activity, and factor VIII von Willebrand factor (vWF) were measured before and 10 minutes after venous occlusion. RESULTS: Patients with RA, with or without rheumatoid vasculitis, had higher baseline PAI levels than control subjects. The difference was statistically significant for patients with RA alone but was not statistically significant for patients with rheumatoid vasculitis. After venous occlusion, t-PA Ag levels increased significantly in normal subjects and patients with RA alone, but not in patients with rheumatoid vasculitis. Plasma levels of vWF were significantly higher in patients with rheumatoid vasculitis than in normal subjects and those with RA alone. In patients with RA alone, baseline vWF correlated positively with t-PA Ag levels, whereas a negative correlation was found between these two parameters in patients with rheumatoid vasculitis. A negative correlation between vWF and t-PA Ag levels after venous occlusion was also found in patients with rheumatoid vasculitis. CONCLUSIONS: Patients with rheumatoid vasculitis showed evidence of vascular damage with increased levels of vWF and impaired t-PA Ag release after venous occlusion, a useful measurement of endothelial reserve to remove fibrin. This may be of pathophysiological importance in the development of vasculitis in these patients.

Adult↗
PubMed1993

Increased whole blood platelet aggregation in patients with Raynaud's phenomenon with or without systemic sclerosis.

Platelet activation may have a pathophysiological role in Raynaud's phenomenon (RP). However, previous studies have shown conflicting results. This may be related to patient selection and the choice of platelet function assay. In this study, we have assessed platelet function of 30 patients with severe RP with (n = 14) or without (n = 16) systemic sclerosis (SSc), using a whole blood platelet aggregation (PA) assay. Raynaud's medication or other drugs which may affect PA were stopped at least 2 weeks previously. Spontaneous whole blood PA and that induced by 0.5 microM adenosine diphosphate and 0.6 and 1 microgram/ml collagen were significantly increased in both groups of patients when compared with controls. There were no significant differences in PA between the 2 groups of patients. Using a more physiological assay, patients with severe RP, whether or not associated with SSc, were shown to have abnormally increased platelet activity. Hyperactive platelets may further impede blood flow in RP.

Adenosine Diphosphate↗
PubMed1992

Effect of dialyzer geometry during hemodialysis with cuprophane membranes.

The effect of dialyzer geometry, both flat plate (FP) and hollow fiber (HF), on platelet and granulocyte activation during dialysis with cuprophane membranes was studied in 12 patients. A subset of six patients was restudied after correction of their anemia with recombinant human erythropoietin (EPO). Granulocyte count and aggregation in vitro fell significantly (P less than 0.01) at 20 minutes of dialysis, followed by a gradual return towards pre-dialysis values at 240 minutes. Malondialdehyde (MDA), a product of free radical reactions generated by activated granulocytes, increased significantly during dialysis [predialysis MDA (median, range): 8.4 (5.8 to 11.6) nmol/ml, 240 minutes MDA: 9.7 (6.6 to 12.5) nmol/ml, P less than 0.01 Wilcoxon test). This increase, however, was not affected by dialyzer geometry or EPO therapy. Neither type of dialyzer was associated with significant platelet loss at the end of dialysis. Whole blood platelet aggregation in vitro (spontaneous and collagen-induced) decreased significantly, (P less than 0.01) during dialysis, the fall in spontaneous aggregation being significantly less following EPO therapy [spontaneous aggregation 240 minutes; pre-EPO: 34 (13 to 52)%; post-EPO 50: (16 to 76)%, P less than 0.01)]. The ratio of the platelet release proteins beta-thromboglobulin and platelet factor 4 increased significantly during dialysis, indicating platelet activation in vivo, although there was no effect of dialyzer geometry or EPO. Factor VIII von Willebrand Factor antigen, a putative marker of endothelial damage, was raised pre-dialysis, and increased further during dialysis, irrespective of dialyzer geometry or EPO. In conclusion, dialyzer geometry had no significant effect on granulocyte and platelet counts and activity during hemodialysis with cuprophane membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Prothrombotic effect of erythropoietin in dialysis patients.

Thrombin-antithrombin III complex concentrations (TAT-III) were measured in 18 anaemic haemodialysis patients treated with erythropoietin (Epo) and in four haemodialysis patients treated with i.v. iron dextran. There was a significant early increase in thrombin-antithrombin III in erythropoietin-treated patients which appeared to be independent of the response to erythropoietin (Epo responders (n = 14), pretreatment TAT-III median (range) 3.10 (2.70-9.10) micrograms/l; maximum TAT-III 19.48 (11.18-60.00) micrograms/l, P less than 0.001, Wilcoxon; Epo non-responders (n = 4), pretreatment TAT-III 3.15 (2.90-4.50) micrograms/l, maximum TAT-III 16.00 (10.31-36.12) micrograms/l, P less than 0.001). This was not seen in iron-dextran-treated patients (Pretreatment TAT-III 2.05 (1.90-9.48) micrograms/l, maximum TAT-III 5.60 (2.10-14.50) micrograms/l). The change was not related to haemoglobin, erythropoietin dose, or method of administration, and was transient in nature, thrombin-antithrombin III returning to pretreatment values after approximately 6 months in all patients (Epo responders 6.0(4.0-9.0) months, TAT-III 2.47 (1.30-9.23) micrograms/l; Epo non-responders 7.0 months, TAT-III 5.04 (2.10-7.00) micrograms/l). Increased thrombin-antithrombin III complex may reflect an effect of erythropoietin on microcirculatory factors, which could be relevant to the occurrence of adverse events during treatment.

Adult↗
PubMed1992

Circadian rhythm of white blood cell aggregation and free radical status in healthy volunteers.

Previous studies have demonstrated circadian rhythms in the onset of thrombotic events, which occur most commonly in the morning, and also in the fibrinolytic activity of the blood which has a peak in the evening and a trough in the morning. There has recently been increasing interest in the role of white blood cells (WBCs) and free radicals (FRs) in thrombosis. No one has yet investigated the potential circadian variation of WBC aggregation and FRs in humans. We studied the circadian rhythm of WBC aggregation and FR status in 10 healthy male volunteers. Six blood samples were collected at 4 hourly intervals from 12:00 (mid-day) until 08:00 the following morning. The volunteers carried out normal daily activities until 00:00 at which time they went to bed and they remained in bed until 08:00. The following were measured on each sample: WBC aggregation; thiobarbituric acid reactive substances (TBARs), plasma thiols (PSH), red cell lysate thiols (LSH), glutathione (GSH) and superoxide dismutase (SOD) which are all altered in the presence of FR activity. The following parameters demonstrated significant circadian rhythms, WBC aggregation p less than 0.001, TBARs p less than 0.015, PSH p less than 0.001, LSH p less than 0.002. WBC aggregation was lowest at 09:00 and highest at 00:00-04:00. TBARs and PSH both had a peak at 16:00 and a trough at 04:00. LSH had a peak at 12:00 and a trough at 08:00. As the behaviour of WBCs and FR status influence the flow properties of blood, a circadian rhythm in WBC function and FR status may contribute to the time of onset of thrombotic diseases. Moreover, with many studies being currently undertaken in this area, our work indicates the need to standardize sample times.

Adult↗
PubMed1991

The effects of thromboxane receptor blockade on platelet aggregation and digital skin blood flow in patients with secondary Raynaud's syndrome.

Raynaud's syndrome (RS) is characterized by intense blood vessel spasm resulting in finger blanching. Treatment primarily involves vasodilation. Thromboxane A2 (TXA2) has been shown to be a potent vasoconstrictor and platelet aggregant. It may be possible to produce a vasodilatory and anti-thrombotic effect by blockade of the TXA2 receptors. ICI 192,605 is a potent TXA2 receptor antagonist and we studied its effects on platelet aggregation and digital blood flow in patients with RS. Sixteen patients with RS completed this double-blind, randomized, placebo controlled study. Each patient was seen on three separate occasions and was given ICI 192,605 (100 mg orally) on one occasion and matching placebo tablets on the other two. We measured platelet aggregation using platelet rich plasma (PRP) stimulated by U46619, a thromboxane (TX) mimetic. The concentration of U46619 required to cause just over 50% platelet aggregation before the administration of either ICI 192,605 or placebo (pre-dose) was noted. The same concentration of U46619 was used to stimulate the PRP sample at 1 h after the administration of ICI 192,605 or placebo (post-dose) and the percentage of platelet aggregation was again noted. Fingertip skin blood flow was also measured 1.25 h post-dose using a laser Doppler flowmeter. Patients were seated in a temperature controlled chamber which was initially heated to 40 degrees C to induce centrally mediated vasodilatation. The temperature was then lowered to 12 degrees C followed by rewarming to 40 degrees C. Steady blood flow values at these temperatures were measured and the rates of cooling and rewarming were also noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Effect of dipyridamole alone and in combination with aspirin on whole blood platelet aggregation, PGI2 generation, and red cell deformability ex vivo in man.

STUDY OBJECTIVE: The aim was to investigate the effects of dipyridamole, aspirin, and a combination of dipyridamole plus aspirin on platelet aggregation in whole blood, PGI2 generation, and red cell deformability ex vivo. SUBJECTS: were 16 male volunteers, aged 22-39 years, mean age, 26.6 years. DESIGN: This was a randomised, double blind, placebo controlled trial. The volunteer received each of the following treatments 10 days apart: dipyridamole 200 mg; aspirin 300 mg; dipyridamole 200 mg plus aspirin 300 mg; matched placebos. MEASUREMENTS AND MAIN RESULTS: Blood was taken for platelet function tests, PGI2 metabolite assay, and red cell deformability before and 2 h after the trial dose was taken. Platelet aggregation was quantified by measuring the fall in single platelet count after stimulation with 2 micrograms.ml-1 collagen or 50 nM platelet activating factor (PAF), or by rollermixing aliquots of blood to initiate spontaneous aggregation. The platelet function tests were completed at 37 degrees C within 10 min of venepuncture. The stable metabolite of PGI2, 6-keto PGF1 alpha, was measured in serum. There was inhibition of spontaneous platelet aggregation by dipyridamole (p less than 0.004), aspirin (p less than 0.005), and the combination of dipyridamole plus aspirin (p less than 0.0001) as compared with placebo. PAF induced platelet aggregation was inhibited by dipyridamole (p less than 0.002) and the combination of dipyridamole plus aspirin (p less than 0.0001) but aspirin alone had no inhibitory effect. Collagen induced platelet aggregation was inhibited by all three treatments: dipyridamole (p less than 0.06), aspirin (p less than 0.0001), and the combination of dipyridamole plus aspirin (p less than 0.0001). PGI2 generation was markedly inhibited by aspirin (p less than 0.0001) and the combination doses (p less than 0.0001) but was unaffected by dipyridamole alone. Of the three active treatments, only dipyridamole alone significantly (p less than 0.001) increased red cell deformability; there was a modest decrease in red cell deformability with aspirin. CONCLUSIONS: The results with PAF support the view that dipyridamole inhibits platelet activation by more than one mechanism; the effect on collagen induced and spontaneous platelet aggregation suggests that the effect of the combination doses is additive and that on red cell deformability the synergy is negative.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Factor VIII von Willebrand factor antigen levels correlate with symptom severity in patients with Raynaud's phenomenon.

We have previously documented raised levels of factor VIII von Willebrand factor antigen (FVIII vWF Ag), an endothelial product, in patients with vascular diseases and suggested that levels of this relate to disease activity. No one has yet investigated patients with Raynaud's phenomenon (RP) alone to see if the severity of vasospastic attacks relates to FVIII vWF Ag. We studied 22 patients with RP. None of these patients fulfilled diagnostic criteria for a connective tissue disease but all had severe symptoms which warranted referral to hospital. We measured the FVIII vWF Ag and the procoagulant factor VIII (FVIII:c) levels in these patients. FVIII:c is not an endothelial product and is released by different mechanisms, thus it forms an active control to FVIII vWF Ag. FVIII vWF Ag measurements were carried out using the Laurell method and FVIII:c was assessed using the technique described by Nilsson. Patients were asked to complete diaries over a 2-week winter period. The frequency and duration of all Raynaud's attacks were recorded. There were significant positive correlations between FVIII vWF Ag and the total number and duration of RP attacks over the 2-week period (P less than 0.005, r = 0.67 and P less than 0.05, r = 0.40, respectively; Spearman's rank correlation). No correlation was found between levels of FVIII:c and the same clinical parameters. It has been suggested that patients with clinical evidence of vascular damage have elevated plasma levels of FVIII vWF Ag. Our present study has demonstrated correlations between FVIII vWF Ag levels and the clinical severity of vasospasm in patients with RP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Circadian variation of endothelial cell function, red blood cell deformability and dehydro-thromboxane B2 in healthy volunteers.

There is a circadian variation in the time of onset of thrombotic disorders. The thrombotic tendency of blood is influenced by many factors including complex interactions between endothelial cells, platelets and red blood cells. We studied the circadian variation of various indices of these cells' functions in 10 young healthy male volunteers. Six blood samples were collected at 4 h intervals from 12.00 until 08.00 the following morning. The volunteers carried out normal daily activities until 00.00 at which time they went to bed. They remained in bed until 08.00 the following morning. The following were measured on each sample: plasma factor VIII von Willebrand factor antigen (FVIII vWF Ag), tissue plasminogen activator activity (tPA), plasminogen activator inhibitor (PAI), prostacyclin stimulating factor (PGI2 SF), fibrinopeptide A (FPA), 11 dehydro-thromboxane B2 (11-dehydro-TXB2) and red cell deformability (RCD). The following parameters demonstrated significant circadian variation: tPA P less than 0.001, PAI P less than 0.04 and 11-dehydro-TXB2 P less than 0.005 (two-way analysis of variance). tPA was highest at 16.00-20.00 and lowest at 08.00; PAI was highest at 08.00 and lowest at 20.00; TXB2 had a peak at 16.00 and trough at 04.00. As the behaviour of endothelial cells and platelets influence the rheological properties of blood, circadian variations in their behaviour may contribute to the time of onset of thrombotic disorders.

Adult↗
PubMed1991

The pharmacokinetics of dermatan sulphate MF701 in healthy human volunteers.

1. The pharmacokinetics of dermatan sulphate MF701 were studied in 12 healthy males after administration of single intravenous bolus (200 mg), intramuscular (100 and 300 mg) and oral (1 g) doses. The study was conducted according to a within-subject crossover design in two paired blocks. 2. Plasma drug concentrations were measured using a competitive binding assay and a range of biological activity assays, including a sensitive catalysed thrombin inhibition test. 3. Following intravenous administration, plasma concentrations of dermatan sulphate determined by competitive binding assay were described by a two-compartment open model with an initial t1/2, in of 0.6 h and a t1/2,z of 7.5 h. Biological activity assays were insufficiently sensitive to detect the second phase, and therefore yielded apparent monoexponential kinetics. 4. After intramuscular injection the apparent bioavailability of dermatan sulphate was 16-20%. Plasma drug concentrations increased in proportion to dose when measured by competitive binding assay. Low concentrations persisted for more than 24 h at the higher dose, and these may prove therapeutically relevant on chronic administration. 5. We confirm that dermatan sulphate is the only glycosaminoglycan known to generate significant plasma concentrations following oral administration. Oral bioavailability was estimated to be 7%.

Adolescent↗