STUDIES ON THE ABSORPTION AND DISTRIBUTION OF CHLORAMPHENICOL

PEDIATRICS ◽  
1951 ◽  
Vol 8 (3) ◽  
pp. 362-367
Author(s):  
RICHARD S. KELLY ◽  
ANDREW D. HUNT ◽  
SYLVIA G. TASHMAN

Chloramphenicol is readily absorbed from the gastrointestinal tract. Peak serum levels, while usually reached within two hours, are occasionally not attained for six or more hours. In general absorption is markedly more rapid than in the case of aureomycin, which seems to be absorbed slowly over a period of several hours. Eleven mg./kg. body weight, which is an adequate single dose of aureomycin, in the case of chloramphenicol produces serum levels too low to be detected by the authors' method. Twenty-two mg./kg. produces two hour levels averaging 8.3 µg./cc. and 44 mg./kg. raises this level to a mean of 22 µg./cc. Rectal administration of perforated chloramphenicol capsules produces peak serum levels approximately one-fifth of those effected with comparable oral dosage. Diffusion of chloramphenicol into cerebrospinal fluid occurs readily and after a few days administration spinal fluid levels, in three cases, were approximately 50% of the serum levels. These data suggest that effective oral dosage of chloramphenicol ranges from 22 to 44 mg./kg./dose and that the antibiotic should be given at 6 to 8 hour intervals.

PEDIATRICS ◽  
1952 ◽  
Vol 9 (5) ◽  
pp. 607-616
Author(s):  
ANDREW D. HUNT ◽  
RICHARD S. KELLEY ◽  
LEWIS L. CORIELL ◽  
M. LOIS MURPHY ◽  
SYLVIA G. TASHMAN ◽  
...  

The absorption of terramycin from the gastrointestinal tract is rather similar to that of aureomycin. Peak levels are low, tend to be achieved in 2 to 6 hours after ingestion, and are prolonged for several hours. Single oral doses of 11 mg/kg. body weight give peak serum levels ranging from 0.20 to 1.95 µg./cc., with a mean of 1.0 µg./cc. Doubling or tripling this single dose did not produce marked increases in serum levels. Dosage of 11 mg./kg. orally every six hours (44 mg./kg./24 hours) resulted in peak serum levels on the third day which were essentially identical with those after the initial dose. However, when a dosage of 33 mg./kg. was given orally every six hours (132 mg./kg./24 hours), marked cumulation in the serum was noted. The mean serum level on the first day on this schedule was 2.7 µg./cc., and on the third day, 8.0 µg./cc. Diffusion into the cerebrospinal fluid in three cases was poor. With spinal fluid and serum levels simultaneously obtained, the spinal fluid levels were ¼, ⅙ and ⅛, respectively of the serum levels. Intravenously administered terramycin in dosage of 6.6 mg./kg. gave peak serum levels at one-half hour, ranging from 10.0 to 12.8 µg./cc. Six hours after injection, serum levels ranged from 1.8 to 4.4 µg./cc., and at 12 hours, from 0.78 to 2.6 µg./cc. Terramycin given rectally in perforated capsules was well tolerated. However, in four patients given 66 mg./kg. by this route, peak serum levels ranged from 0 to 1.0 µg./cc. Recommended terramycin dosage: (a) Oral: 11 mg./kg./dose every six hours (44 mg./kg./24 hours). Adequate antibacterial serum levels for most susceptible organisms are produced with this dosage. Increasing the dosage to 33 mg./kg./dose every six hours (132 mg./kg./24 hours) may be done in cases when high serum levels seem indicated. (b) Intravenous: 6.6 to 11 mg./kg./dose every 6 to 8 hours.


PEDIATRICS ◽  
1981 ◽  
Vol 67 (3) ◽  
pp. 387-388
Author(s):  
Michael E. Speer ◽  
Edward O. Mason ◽  
John T. Scharnberg

Simultaneous serum and CSF samples were obtained following the intramuscular administration of 50,000 units/kg of aqueous procaine penicillin G in 25 neonates. Penicillin activity was detected in the sera and CSF of all patients. Peak serum levels were noted at four hours (mean ± SEM, 17.1 ± 6.3 µg/ml). Peak CSF levels were noted at 12 hours (0.70 ± 0.35 µg/ml). The serum level at 24 hours was 2.1 ± 0.98 µg/ml (range, 0.2 to 5.8 µg/ml); the CSF level at 24 hours was 0.12 ± 0.05 µg/ml (range, 0.03 to 0.27 µg/ml). These results demonstrate that spirocheticidal levels (≥0.03 µg/ml) are achieved for at least 24 hours in the CSF following the intramuscular administration of aqueous procaine penicillin G in neonates.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5264-5264
Author(s):  
Stefan Fruehauf ◽  
Timon Seeger ◽  
Julian Topaly ◽  
Anthony D. Ho ◽  
Hartmut Goldschmidt

Abstract Autologous peripheral blood stem cell (PBSC) transplantation leads to significant prolongation of survival in patients with different malignancies. For PBSC mobilization a combination of myelosuppressive chemotherapy and granulocyte colony stimulating factor (G-CSF) are administered. The optimal application of G-CSF is twice daily. New G-CSF formulations with prolonged half-life carry the promise of reduced patient strain, increased compliance and via continuously high G-CSF serum levels possibly improved PBSC mobilization. We initiated a study with pegfilgrastim-supported mobilization chemotherapy in stage II and III myeloma patients. Patients received up-front treatment with three cycles of vincristin, doxorubicin, dexamethason (VAD) or thalidomide, doxorubicin, dexamethason (TAD). The mobilization regime consisted of four days chemotherapy with cyclophosphamide 1g/m2 day1, doxorubicin 15mg/m2 day 1–4, dexamethason 40 mg d 1–4 p.o. (CAD) and a single administration of 12 mg pegfilgrastim subcutaneously on day five. 25 patients (median age 57, 12 female, 13 male) received pegfilgrastim and leukapheresis was started 6–17 days (mean 10 days) after treatment with a range of maximum CD34 cell count between 7,2 and 842 (mean: 119) CD34+ cells/μl peripheral blood. After leukapheresis 6.2 * 10e6 to 40.5 * 10e6 (mean 13.8 *10e6) CD34+ cells per kilogram body weight were collected. 11 patients achieved the target number of 7.5 * 10e6 CD34+ cells per kilogram body weight during a single apheresis, while 5 patients needed two, 7 patients needed three and 2 patients needed four apheresies on consecutive days. 3 patients required additional administration of filgrastim. 2 patients received 6 mg pegfilgrastim off study. Both achieved sufficient numbers of CD34+ cells (12.7 and 20.8 * 10e6 CD34+ per kg BW). There were only minimal adverse effects. Four patients reported of bone pain or nausea. Mobilization failures did not occur in this patient population. To date, 16 patients have been transplanted with a mean of 6,03* 10e6 CD34+ per kg BW (range 2,4 to 13,5). Reconstitution (reaching a leukocyte count of >1,0/nl) was reached within a mean of 13 days (range 11–21). On the basis of these first results we conclude that a single dose application of 12 mg pegfilgrastim after CAD treatment allows collection of more than 3 autografts in two or less apheresis session in the majority of myeloma patients. Reduction of apheresis sessions is a significant clinical cost-effectiveness end point in PBPC mobilization.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1644-1644 ◽  
Author(s):  
Jean-Francois Larouche ◽  
Marc Bergeron ◽  
Grace Hampson ◽  
Tim Illidge ◽  
Robert Delage

Abstract Abstract 1644 INTRODUCTION: Rituximab penetration in central nervous system is largely unknown in human. Experiments in monkeys showed that 0,1% of serum rituximab concentration was achieved in cerebrospinal fluid. Reports in patients are limited (Rubenstein JL, Blood 2003 and Petereit HF, Multiple Sclerosis 2009). They demonstrated similar low levels of cerebrospinal fluid penetration with standard dose (375 mg /m2) rituximab in patients with central nervous system (CNS) lymphoma or multiple sclerosis. METHOD: We conducted a phase 2 trial in patients with primary CNS lymphoma. Patients were treated with an intravenous combination of high dose methotrexate (8 g/m2), high dose cytarabine (2 g/m2) and high dose rituximab (750 mg/m2 every 1–2 weeks × 13 infusions). We obtained from four patients paired cerebrospinal fluid and serum samples and rituximab concentration were determined in each. Samples were collected at different time points just before rituximab infusion and represent trough levels. RESULTS: 11 cerebrospinal fluid samples were available and their 11 paired serum samples. Mean cerebrospinal fluid and serum levels were 2,04 ug/mL (0,49–4,08) and 297,09 ug/mL (211,26–504,47) respectively. Mean cerebrospinal fluid levels were 0,71% (0,18–1,5%) of serum levels. No relationship was made between cerebrospinal fluid level and the number of rituximab dose administered. CONCLUSION: In patients with primary CNS lymphoma receiving high dose 1–2 weekly rituximab. cerebrospinal fluid concentration achieve is low compared to serum levels. However, administration of higher dose of intravenous rituximab can increase penetration in central nervous system but its clinical impact is unknown as cerebrospinal fluid levels are still low. Disclosures: No relevant conflicts of interest to declare.


1973 ◽  
Vol 1 (6) ◽  
pp. 530-533 ◽  
Author(s):  
C A Fernandez ◽  
J P Menezes ◽  
J Ximenes

The effect of food on the absorption of pivampicillin hydrochloride and ampicillin potassium was compared in a single-dose, 3-way, cross-over study in fifteen healthy adult subjects. The antibiotics were given in their recommended doses in capsule form: 350 mg of pivampicillin and 500 mg of ampicillin. Ampicillin was administered in the fasting state while pivampicillin was administered both in the fasting state and during a standardized cooked breakfast. The presence of food caused a substantial decrease and delay in the absorption of pivampicillin. Pivampicillin administered during a meal, as recommended to minimize gastro-intestinal irritation, resulted in lower serum levels than those attained with ampicillin given without food. The average peak serum levels of pivampicillin taken during meals was 3.34 mcg/ml compared to 4.47 mcg/ml with ampicillin given in the fasting state. The total antibiotic coverage indicated by time-absorption curves was also considerably lower with pivampicillin than with ampicillin under conditions simulating those recommended during clinical use by the respective manufacturers.


2010 ◽  
Vol 54 (9) ◽  
pp. 3985-3987 ◽  
Author(s):  
Charalampos Antachopoulos ◽  
Matti Karvanen ◽  
Elias Iosifidis ◽  
Britt Jansson ◽  
Diamantis Plachouras ◽  
...  

ABSTRACT Using a liquid chromatography-tandem mass spectrometry method, the serum and cerebrospinal fluid (CSF) concentrations of colistin were determined in patients aged 1 months to 14 years receiving intravenous colistimethate sodium (60,000 to 225,000 IU/kg of body weight/day). Only in one of five courses studied (a 14-year-old receiving 225,000 IU/kg/day) did serum concentrations exceed the 2 μg/ml CLSI/EUCAST breakpoint defining susceptibility to colistin for Pseudomonas and Acinetobacter. CSF colistin concentrations were <0.2 μg/ml but increased in the presence of meningitis (∼0.5 μg/ml or 34 to 67% of serum levels).


2002 ◽  
Vol 46 (1) ◽  
pp. 188-190 ◽  
Author(s):  
Philippe Cottagnoud ◽  
Cynthia M. Gerber ◽  
Marianne Cottagnoud ◽  
Martin G. Täuber

ABSTRACT In experimental meningitis a single dose of gentamicin (10 mg/kg of body weight) led to gentamicin levels in around cerebrospinal fluid (CSF) of 4 mg/liter for 4 h, decreasing slowly to 2 mg/liter 4 h later. The CSF penetration of gentamicin ranged around 27%, calculated by comparison of areas under the curve (AUC in serum/AUC in CSF). Gentamicin monotherapy (−1.24 log10 CFU/ml) was inferior to vancomycin monotherapy (−2.54 log10 CFU/ml) over 8 h against penicillin-resistant pneumococci. However, the combination of vancomycin with gentamicin was significantly superior (−4.48 log10 CFU/ml) compared to either monotherapy alone. The synergistic activity of vancomycin combined with gentamicin was also demonstrated in vitro in time-kill assays.


2016 ◽  
Vol 13 (6) ◽  
pp. 654-662 ◽  
Author(s):  
Carlo Wilke ◽  
Frank Gillardon ◽  
Christian Deuschle ◽  
Evelyn Dubois ◽  
Markus A. Hobert ◽  
...  

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Jan Martin ◽  
Eva Plank ◽  
Bettina Jungwirth ◽  
Alexander Hapfelmeier ◽  
Armin Podtschaske ◽  
...  

Abstract Background Neuroactive steroids seem to be implicated in a variety of neurophysiological and behavioral processes, such as sleep, learning, memory, stress, feeding and aging. Numerous studies have also addressed this implication in various cerebral disorders and diseases. Yet, the correlation and association between steroids in the periphery, e.g. blood, and the central compartments, e.g. cerebrospinal fluid (CSF), have not yet been comprehensively assessed. As the brain is not directly accessible, and the collection of human CSF usually requires invasive procedures, easier accessible compartments, such as blood, have always attracted attention. However, studies in humans are scarce. In the present study we determined estradiol, progesterone and testosterone levels in CSF and serum of 22 males without cerebral disorders or diseases. Results Samples were taken under conditions corresponding closest to basal conditions with patients expecting only spinal anesthesia and minor surgery. All samples per patient were collected concomitantly. Total estradiol, progesterone and testosterone concentrations were measured by electro-chemiluminescence immunoassay. The strength of correlation was assessed by Spearman’s rank correlation coefficient. Correlation analysis revealed merely weak to very weak correlations for estradiol, progesterone and testosterone respectively between the CSF and serum compartments. Conclusions Total steroid levels of estradiol, progesterone and testosterone in CSF and serum of males without neurological disorders were determined. Weak to very weak correlations between CSF and serum were found thus suggesting that concentrations in the periphery do not parallel concentrations in the central compartments. Further research is needed to clarify to what extent and under which conditions serum levels of estradiol, progesterone and testosterone may possibly serve as a biomarker reflecting the respective concentrations in the CSF or in the brain.


Author(s):  
Julio H. Garcia ◽  
Janice P. Van Zandt

Repeated administration of methyl alcohol to Rhesus monkeys (Maccaca mulata) by intragastric tube resulted in ultrastructural abnormalities of hepatocytes, which persisted in one animal twelve weeks after discontinuation of the methyl alcohol regime. With dosages ranging between 3.0 to 6.0 gms. of methanol per kg. of body weight, the serum levels attained within a few hours averaged approximately 475 mg. per cent.


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