Nomogram for individualizing supplementary iron doses during erythropoietin therapy in haemodialysis patients.

AIMS: An adequate iron supplement is crucial not only for prompt erythropoiesis but also for the restoration of tissue iron reserves in haemodialysis patients receiving recombinant human erythropoietin (r-HuEPO). An attempt was made to establish a comprehensive nomogram that allows individualization of intravenous (i.v.) iron doses according to patients' body weights, the initial status of tissue iron reserves and desired increases in haemoglobin levels. MATERIALS AND METHODS: Clinical and laboratory data retrieved from 95 haemodialysis patients who received r-HuEPO with or without iron supplements for at least 12 weeks were used to construct the nomogram. It was assumed that the administered iron was either incorporated into newly synthesized haemoglobin and tissue iron reserves or eliminated from the body at a constant rate. Tissue iron reserves of the patients were estimated by serum ferritin levels using van Wyck's equation (Kidney Int., 1989, 35, 712). The rate of iron loss in the patients was estimated by the data obtained from 15 of the above patients who exhibited stable haemoglobin levels but decreases in serum ferritin levels with no iron supplements. The validity of the equation was ascertained by comparing the measured serum ferritin levels at the end of r-HuEPO therapy and those predicted by the nomogram. The proposed nomogram was then validated prospectively in 24 haemodialysis patients to determine whether the nomogram-recommended iron doses would increase both haemoglobin and serum ferritin levels within 12 weeks. RESULTS: The mean (+/-SD) iron loss of haemodialysis patients was calculated to be 10.5 +/- 7.4 mg/week. There was a significant correlation (r=0.77, P < 0.001) between the measured serum ferritin levels, an index of tissue iron reserves, at the end of r-HuEPO therapy and those predicted by the equations used for formulating the nomogram. The prospective study indicated that the nomogram-recommended supplementary iron doses attained haemoglobin and serum ferritin levels of > 95 g/L and >100 microg/L in 79 and 50% of the patients, respectively, within 12 weeks. CONCLUSION: The present nomogram may be useful for individualizing supplementary i.v. iron doses for haemodialysis patients undergoing r-HuEPO therapy.

The effects of rifampicin on the pharmacokinetics and pharmacodynamics of orally administered nilvadipine to healthy subjects.

AIMS: To study the effects of rifampicin on the pharmacokinetics and pharmacodynamics of nilvadipine. METHODS: Five healthy adult volunteers received nilvadipine (4 mg) orally before and after a 6 day treatment with rifampicin. Blood and urine were collected and assayed for plasma nilvadipine and urinary 6beta-hydroxycortisol and cortisol. RESULTS: The treatment with rifampicin reduced the mean (+/- s.d.) AUC of nilvadipine from 17.4 +/- 8.4 to 0.6 +/- 0.4 microg l-1 h (mean difference -16.8 microg l-1 h, 95% CI -9.4, 24.2 microg l-1 h). While the administration of nilvadipine alone elicited a significant (P < 0.05) hypotensive (mean difference for diastolic blood pressure -8 mmHg, 95% CI -4, -12 mmHg) and reflex tachycardia (mean difference 5 beats min-1, 95% CI 1, 9 beats min-1), the treatment with rifampicin abolished these responses. The urinary 6beta-hydroxycortisol/cortisol ratio showed a significant (P < 0.05) increase from 10.3 +/- 4.0 to 50.3 +/- 24.6 by rifampicin: mean difference 40.1, 95% CI 20.4, 59.8. CONCLUSIONS: Because rifampicin may greatly decrease the oral bioavailability of nilvadipine, caution is needed when these two drugs are to be coadministered.

Effects of oral supplementation with evening primrose oil for six weeks on plasma essential fatty acids and uremic skin symptoms in hemodialysis patients.

Abnormalities in plasma composition of essential fatty acids (EFAs) may be associated with the etiology of pruritus and other skin problems in patients undergoing hemodialysis. To study whether an oral supplementation with omega-6 (n-6) EFAs would restore deranged plasma EFAs and ameliorate skin symptoms, 9 and 7 dialysis patients were randomly assigned to receive either gamma-linolenic acid (GLA)-rich evening primrose oil (EPO) or linoleic acid (LA) (2 g/day each) for 6 weeks. Plasma concentrations of EFA were analyzed by gas chromatography and uremic skin symptoms were assessed for dryness, pruritus and erythema by questionnaire and visual inspection in a double-blind manner. The patients given EPO exhibited a significant (p < 0.05) increase in plasma dihomo-gamma-linolenic acid (a precursor of anti-inflammatory prostaglandin E1) with no concomitant change in plasma arachidonic acid (a precursor of pro-inflammatory prostaglandin E2 and leukotriene B4). In contrast, those given LA exhibited a significant (p < 0.05) increase in LA but not in any other n-6 EFAs, whereas they exhibited a significant (p < 0.05) decrease in plasma docosahexaenoic acid. The patients given EPO showed a significant (p < 0.05) improvement in the skin scores for the three different uremic skin symptoms over the baseline values and a trend toward a greater improvement (0.05 < p < 0.1) in pruritus scores than those given LA. Results indicate that GLA-rich EPO would be a more favorable supplemental source than LA in terms of shifting eicosanoid metabolism toward a less inflammation status through modifying plasma concentrations of their precursor n-6 EFAs. Further studies are required to confirm the efficacy and safety of EPO therapy for the treatment of uremic pruritus.