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M V Relling

Publications and source records attributed to M V Relling.

132 records · Page 8Linked to original sources
PubMed1987

Pharmacokinetics of anticancer drugs in children.

Interpatient pharmacokinetic variability normally observed in adults is often of even greater magnitude in paediatric patients because of age-related maturation of physiological processes responsible for drug disposition. Several antineoplastic agents have shown age-related changes, including alterations in volume of distribution, hepatic (doxorubicin, cyclophosphamide), and renal (bleomycin, methotrexate) clearances. These differences in pharmacokinetics as a function of age alter systemic exposure to chemotherapy, and may alter the efficacy and toxicity profile for standard doses of antineoplastic drugs. The relationship of systemic exposure to toxicity has been most clearly defined for methotrexate. Clinical monitoring of methotrexate serum concentrations, and adjustment of folinic acid dosages and duration of rescue based on methotrexate disposition is now routine. More recently, pharmacodynamic data have been published for high-dose methotrexate, epipodophyllotoxins, cisplatin, and cytarabine (cytosine arabinoside), indicating a relation between drug disposition and toxicity or efficacy. Collectively, these data suggest that the pharmacokinetics of many anticancer drugs in children is different from adults, and that variability in drug disposition may have an important influence on toxicity or efficacy.

Adult↗
PubMed1987

Clinical pharmacodynamic studies of high-dose methotrexate in acute lymphocytic leukemia.

As the intensity of cancer chemotherapy has been reported to influence clinical response for several drug-sensitive cancers, we have investigated the relation between systemic exposure to high-dose methotrexate (HDMTX) and clinical response in childhood acute lymphocytic leukemia (ALL). A total of 108 consecutive, previously untreated children with "standard-intermediate risk" ALL were randomized to receive postinduction therapy with HDMTX (1000 mg/m2 iv over 24 hours weekly for 3 weeks, then every 6 weeks for 72 weeks), superimposed on conventional therapy with low-dose 6-mercaptopurine (6MP; 50 mg/m2 orally per day) and methotrexate (MTX; 25 mg/m2 orally per week). The systemic clearance of HDMTX ranged from 40 to 131 ml/minute/m2 among these patients, yielding MTX steady-state plasma concentrations (Cpss) ranging from 9.3 to 25.4 microM during the infusion. The group of patients (n = 59) with median MTX Cpss less than 16 microM during the HDMTX infusion had a higher probability of having any relapse than patients (n = 49) with MTX Cpss greater than 16 microM (P less than 0.05). In a previously reported univariate analysis, patients with MTX Cpss less than or equal to 16 microM were 3.2 times more likely to relapse on therapy (P = 0.01) and 6.9 times more likely to have a hematologic relapse on therapy (P = 0.001). Multivariate and stepwise Cox's regression analyses indicated that MTX Cpss retains its prognostic importance even when other prognostic variables (i.e., DNA Index, WBC, hemoglobin) are considered.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1986

Drug-induced hemorrhagic cystitis.

A case of ticarcillin-induced hemorrhagic cystitis is presented, and the literature on drug-induced hemorrhagic cystitis is reviewed. A 12-year-old white boy with cystic fibrosis was hospitalized for an exacerbation of his pulmonary disease. Laboratory tests on admission showed an elevated white blood cell (WBC) count, 10-20 WBCs per high-power field (HPF) in urine, and normal BUN and serum creatinine. The patient was given ticarcillin i.v. (as the disodium salt) (final dosage of 320 mg/kg/day) in divided doses every six hours and netilmicin i.v. (as the sulfate salt) (final dosage of 4 mg/kg every eight hours). On day 7 the patient complained of painful urination, and urinalysis showed a 10-20 WBCs/HPF and 2-5 red blood cells (RBCs)/HPF. Two days later, the patient had gross hematuria, and urinalysis revealed 10-20 WBCs/HPF and 10-20 RBCs/HPF. Ticarcillin and netilmicin were discontinued and the patient's symptoms abated within 48 hours. Repeat urinalysis on day 11 showed no RBCs and 10-20 WBCs/HPF, with no casts or protein. Three months later, the patient was again hospitalized for an exacerbation of his cystic fibrosis. He was placed on tobramycin sulfate i.v. and ticarcillin i.v. (340 mg/kg/day). After the fourth dose of ticarcillin, the patient again complained of urinary pain and frequency and also reported gross hematuria. Urinalysis showed bacteria, 2-5 WBCs/HPF, and 5-10 RBCs/HPF; however, urine cultures were negative. Ticarcillin was discontinued and cefoxitin sodium i.v. was started. The patient's symptoms resolved within 36 hours, and a urinalysis on the fourth hospital day was normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMedDate not supplied

CYP2D6, N-acetylation, and xanthine oxidase activity in cystic fibrosis.

STUDY OBJECTIVE: To determine the activity of CYP2D6, N-acetylation, and xanthine oxidase, three drug-metabolizing enzyme systems, in patients with cystic fibrosis and compare the findings with those in individuals without the disease. DESIGN: Prospective cohort study. SETTING: General pediatrics service. PATIENTS: Fifty-nine patients with cystic fibrosis and 480 healthy Caucasian volunteers. INTERVENTIONS: Enzyme activity was determined based on urinary molar metabolite ratios of caffeine and dextromethorphan probes. MEASUREMENTS AND MAIN RESULTS: The percentage of poor metabolizers of CYP2D6 in patients with cystic fibrosis was not different from that in the control group (p = 0.45). N-Acetylation activity was significantly lower in the patients (p = 0.007), but no statistically significant difference was found in xanthine oxidase activity (p = 0.12). CONCLUSION: The activity of these drug-metabolic pathways does not appear to be increased in cystic fibrosis. Whether the activity of other pathways is increased, thus providing a partial explanation for the generally increased drug clearance in this disease, remains to be determined.

Acetylation↗