Pediatric pharmacology (New York, N.Y.)最新文献

{"title":"Lack of pharmacological active saliva levels of caffeine in breast-fed infants.","authors":"R Hildebrandt,&nbsp;U Gundert-Remy","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Caffeine, which is used for the treatment of apnoea in premature newborns, is known to be excreted into breast milk. However data on the amount of caffeine transferred to the breast-fed infant and on caffeine concentrations in the baby are lacking. In 18 healthy breast-feeding women caffeine concentrations in breast milk were measured 2 and 4 hours after the intake of coffee (145.8 mg caffeine, mean +/- sd, n = 18). For an estimation of kinetic parameters (eg, AUC), additional saliva samples were collected up to 6 hours after coffee intake. The daily caffeine intake of the infants was calculated from the average breast-milk concentration (AUCsaliva X milk/saliva ratio/24 hours) as average milk concentration X daily milk volume. From nine of the babies (aged 20 days to 19 weeks) at least one saliva sample could be obtained. The ratio milk/saliva was found to be 0.90 +/- 0.20 (mean +/- sd, n = 18) and the average breast-milk concentration was 0.82 +/- 0.29 mg/L (mean +/- sd, n = 18). The daily caffeine intake of the infants was calculated to range from 0.027 to 0.203 mg/kg/day. The caffeine concentrations measured in the babies ranged from less than 0.05 to 0.75 mg/L. Hence it can be concluded that the amount of caffeine ingested by the children is small compared to the therapeutic dose if usual amounts of coffee are taken by the mothers.</p>","PeriodicalId":77932,"journal":{"name":"Pediatric pharmacology (New York, N.Y.)","volume":"3 3-4","pages":"237-44"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17732296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative pharmacological evaluation of oral benzathine penicillin G and phenoxymethyl penicillin potassium in children.","authors":"K Fujita,&nbsp;H Sakata,&nbsp;K Murono,&nbsp;H Hasegawa,&nbsp;M Takimoto,&nbsp;H Yoshioka","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Serum penicillin concentrations and urine excretion rates of oral benzathine penicillin G and phenoxymethyl penicillin potassium were evaluated in children. Mean peak serum concentration of 0.134 microgram/ml of benzathine penicillin G and 1.018 microgram/ml of phenoxymethyl penicillin potassium were measured at 125 and 35 min. The mean half-life times were 1.36 and 0.74 hr, and for area under the curve, the values were 0.34 and 1.68 microgram . hr/ml for benzathine penicillin G and phenoxymethyl penicillin potassium groups, respectively. Phenoxymethyl penicillin potassium had more reliable pharmacokinetic properties and would be the preferred forms of oral penicillin. However, all patients receiving penicillin G had penicillinemia, which was enough to inhibit most strains of Streptococcus pyogenes for a longer period than phenoxymethyl penicillin potassium. Palatability of phenoxymethyl penicillin is less than for benzathine penicillin G; the latter may be used for children in whom compliance may be a problem.</p>","PeriodicalId":77932,"journal":{"name":"Pediatric pharmacology (New York, N.Y.)","volume":"3 1","pages":"37-41"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17477630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzyme induction in neonates after fetal exposure to antiepileptic drugs.","authors":"D Rating,&nbsp;E Jäger-Roman,&nbsp;H Nau,&nbsp;W Kuhnz,&nbsp;H Helge","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The 13C-AP breath test is shown to be a convenient, noninvasive method to monitor velocity and capacity of P450-dependent AP N-demethylation in infancy and childhood. According to 13C-AP breath tests, neonates have a very low capacity to eliminate 13CO2, which is only 15 to 21% of the activity in adults. During the first year of life AP N-demethylation increases to reach its maximum at about 2 years; afterwards a slight decrease occurs. In 25 neonates exposed prenatally to different antiepileptic drugs 13C-AP breath test was efficiently used to prove that cytochrome AP N-demethylation was considerably stimulated. After primidone/phenobarbitone, especially in combination with phenytoin, 13C elimination reaches and even surpasses the range for older children. Valproate exposure during fetal life is not consistently followed by a significant increase in AP N-demethylation. The enzyme induction demonstrated by 13C-AP breath test was often accompanied by accelerated metabolic clearance and shortened half-life times of transplacentally acquired antiepileptic drugs. There was good agreement between 13C-AP breath tests and pharmacokinetic data for primidone/phenobarbitone but not for phenytoin. In contrast, in the case of phenytoin exposure during pregnancy the pharmacokinetic parameters and the 13C breath test data will transport very different informations about enzyme induction in these neonates.</p>","PeriodicalId":77932,"journal":{"name":"Pediatric pharmacology (New York, N.Y.)","volume":"3 3-4","pages":"209-18"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17489161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theophylline for chronic asthma: rationale for treatment, product selection, and dosage schedule.","authors":"M Weinberger,&nbsp;L Hendeles","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Although theophylline has been available for over 50 years, only in the last 10 years has an understanding of its pharmacodynamics and pharmacokinetics permitted its use with optimal efficacy and safety. Serum concentrations between 10 and 20 mcg/ml stabilize the hyperreactive airways that characterize asthma as measured by exercise-induced bronchospasm and clinical suppression of asthmatic symptoms, even among those patients not sufficiently controlled with bronchodilators alone who consequently require inhaled or oral corticosteroid therapy. Careful dosage titration prevents adverse effects, especially when final dosage is guided by measurement of serum concentration. Large interpatient variability in dose requirements is seen, but there is normally little intrapatient variability except when physiologic abnormalities or drug interactions alter the elimination of theophylline. Rapid elimination, rapid absorption from conventional products, and the narrow therapeutic range for theophylline result in clinically important fluctuations in serum concentration and consequent effect unless unrealistically short dosing intervals are maintained or reliable slow-release formulations are used. Slow-release theophylline products vary, however, and performance often does not match the manufacturer's claims. Assessment requires characterization of absorption rate, which then allows prediction of fluctuations in serum concentration at specified dose intervals and defined rates of elimination.</p>","PeriodicalId":77932,"journal":{"name":"Pediatric pharmacology (New York, N.Y.)","volume":"3 3-4","pages":"273-85"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17489164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amikacin doses in very low birthweight newborns.","authors":"C G Prober,&nbsp;P Rajchgot","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77932,"journal":{"name":"Pediatric pharmacology (New York, N.Y.)","volume":"3 2","pages":"125-6"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17729602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics of dexamethasone in children.","authors":"O Richter,&nbsp;B Ern,&nbsp;D Reinhardt,&nbsp;B Becker","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A pharmacokinetic data analysis of plasma level data for dexamethasone obtained from children with various diseases and healthy adults was performed. A total of 33 subjects participated in the study. The results show: The pharmacokinetics of dexamethasone can be described satisfactorily within the frame of classic linear pharmacokinetic theory. The variance of important pharmacokinetic parameters is large. Therefore, if a close relationship between drug levels and therapeutic and adverse effects exists, which still has to be proved, optimal individual dosage regimens have to be calculated, guided by drug-level monitoring. When treating newborns, one should be aware that high drug levels are likely to occur, possibly necessitating a dose reduction.</p>","PeriodicalId":77932,"journal":{"name":"Pediatric pharmacology (New York, N.Y.)","volume":"3 3-4","pages":"329-37"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17732302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug therapy in childhood: what has been done and what has to be done?","authors":"H Bartels","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Exactly 30 years ago the German pediatrician Dost introduced the concept of pharmacokinetics into clinical and experimental research. In the following years this concept prompted a rapidly increasing understanding of the mechanisms of drug disposition and of host factors as major determinants of drug concentration and, in consequence, of drug effect within the organism. This has led to a burgeoning new discipline--clinical pharmacology. However, the pharmacokinetic approach was, with few exceptions, not particularly cherished by the pediatricians, until dramatic clinical accidents, such as the chloramphenicol-gray syndrome and the thalidomide-phocomelia tragedies occurred, which highlighted the pharmacokinetic, and pharmacodynamic, features of the growing organism, especially of the fetus, newborn, and young infant. In the 1970s, the explosive development of sensitive and specific methods for the analysis of nearly all drugs in body fluids and tissues and the great progress in computer technology induced an enormous progress in clinical pharmacokinetics making age-related drug and dosage recommendations possible, which were based on scientific data, and initiating therapeutic drug monitoring. However, years ago, in 1965, von Harnack and others published pediatric drug dosage recommendations based on empiric data realizing that, for many drugs, an appropriate dosage schedule can be achieved when the drug dose is calculated according to body surface area rather than to body weight. While advances in pediatric pharmacokinetics have been proceeding at a rapid pace during the last decade, it is quite evident that the progress in pharmacodynamics has lagged far behind the research and attention paid to pharmacokinetics. For the future increasing work concerning the quantitation of clinical effects in correlation to drug dosage and drug level is urgently needed. That holds true for short-term and for long-term clinical effects of drugs given to newborns, infants, and children, as well as for adverse and for desired therapeutic effects of drugs administered to an unborn via his mother. Undoubtedly, quantitative determination of clinical drug effects is much more difficult than quantitation of pharmacokinetics, not only for technical, but also for ethical reasons. Moreover, pharmacodynamic studies in long-term treatment of chronically ill children are complicated by the problem of the patient's compliance. However, the rapid progress in pediatric oncology in the past is an impressive example for the usefulness of controlled clinical trials based on pharmacodynamic rather than pharmacokinetic criteria.</p>","PeriodicalId":77932,"journal":{"name":"Pediatric pharmacology (New York, N.Y.)","volume":"3 3-4","pages":"131-43"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17732396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics of propylthiouracil in children and adolescents with Graves disease after a single oral dose.","authors":"A Okuno,&nbsp;T Taguchi,&nbsp;F Inyaku,&nbsp;K Yano,&nbsp;Y Suzuki","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Pharmacokinetics of propylthiouracil after a single oral dose were studied in six pediatric patients with Graves disease, with respect to influence of food intake. Propylthiouracil administration in the fasting state induced a rapid rise of plasma level reaching a peak of 30 to 60 min. Peak values ranged from 7.2 to 18 micrograms/ml with administered dose (100 to 280 mg/m2 BSA) and plasma half-life was 1.3 +/- 0.41 hr (mean +/- SD). Single compartment model with first order absorption showed excellent fit to the data obtained in the fasting state, but not in the fed state. Most individuals showed marked difference in the pattern of propylthiouracil concentration-time curves between the fasting and the fed state. Food intake prior to the drug ingestion was associated with lower and delayed peak and variable AUC values. These results indicate that propylthiouracil administration in the fasting state is more advisable for obtaining a consistent bioavailability.</p>","PeriodicalId":77932,"journal":{"name":"Pediatric pharmacology (New York, N.Y.)","volume":"3 1","pages":"43-7"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17743007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Essential laboratory determinations for monitoring high-dose methotrexate treatment with citrovorum factor rescue.","authors":"H Jürgens,&nbsp;W Ebell,&nbsp;R Bachmann,&nbsp;I Kupke,&nbsp;O Richter,&nbsp;A Andräs,&nbsp;U Göbel","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The use of high-dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) has considerably improved the prognosis of some pediatric malignancies. Massive doses of methotrexate (mtx) may lead to severe or even lethal toxicity. Safe administration of this regimen requires a wide pattern of laboratory tests as well as clinical supervision. One hundred and eighteen courses of HDMTX (12 gm/m2 over 6 hours iv) with CFR administered to 12 patients were analysed for changes of routine laboratory tests 0, 6, 24, 48, and 72 hours following infusion. Hgb, WBC, and platelets on average showed no change during the 72 hours follow-up period. Serum SGOT and SGPT were elevated with a maximum 24 hours following infusion and slowly returned to normal. The increase of serum LDH values were less marked and reached a maximum at 48 hours; changes of serum y-GT values were not significant. Evaluation of the elimination of mtx from serum in each individual patient throughout 14 sequential mtx courses gave no evidence of a prolonged serum half life due to impaired renal mtx clearance. There was also no evidence of enzyme induction in the liver resulting in a shortened serum half-life. Changes of serum enzymes also were not increasing throughout treatment. Careful monitoring of serum mtx levels is mandatory when HDMTX with CFR treatment is administered. Elevation of blood urea nitrogen and creatinine levels within 24 hours following mtx treatment identify the patient at risk for slow mtx elimination and severe toxicity requiring salvage by adequate doses of citrovorum factor.</p>","PeriodicalId":77932,"journal":{"name":"Pediatric pharmacology (New York, N.Y.)","volume":"3 3-4","pages":"157-65"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17666893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics of moxalactam in anuric children and during hemodialysis.","authors":"S L Kaplan,&nbsp;P L Berry,&nbsp;E O Mason,&nbsp;W G Kramer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Pharmacokinetics of moxalactam were determined in children with chronic renal failure during a 4-hour hemodialysis or an interdialytic period following a 50 mg/kg dose. Mean elimination half-life during dialysis was 3.9 hours compared to 12.9 hours during the interdialytic period. Mean clearance of moxalactam was 86 ml/minute during hemodialysis and 25 ml/minute between dialysis. Mean dialyzer clearance of moxalactam was 45 ml/minute. The mean fraction of moxalactam removed during a 4-hour hemodialysis was 18% in nine children. In anuric children, a 50 mg/kg dose of moxalactam should be given every 48 hours in an interdialytic period and a 25 mg/kg dose given after each dialysis.</p>","PeriodicalId":77932,"journal":{"name":"Pediatric pharmacology (New York, N.Y.)","volume":"3 1","pages":"29-36"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17702179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}