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PubMed1981

On the pharmacokinetics of domperidone in animals and man II. Tissue distribution, placental and milk transfer of domperidone in the Wistar rat.

Tissue distribution, placental transfer and transition into milk of the gastrokinetic drug domperidone were studied in the Wistar rat after i.v. or p.o. administration of the labelled compound at 2.5 mg/kg. Whole-body autoradiography and liquid scintillation counting were used to investigate the tissue localization of domperidone in pregnant and non-pregnant rats. In fasted rats, tissue levels were maximal within 15 minutes after either route. In non-fasted animals peak time occurred 30 minutes after oral treatment. Large amounts of radioactivity were present in the stomach, and in the bilious contents of the intestine. High activity was further detected in the liver, kidney, lung and some glandular tissues. After a rapid initial decrease radioactivity was eliminated with a half-life of 8-10 hours. Except for brain and testes, plasma levels were markedly lower than corresponding tissue levels. At 1 hour placental levels were 2-2.7 times higher and foetal concentrations 2.1-2.5 times lower than maternal plasma levels. The placentae and foetuses predominantly contained unchanged domperidone. At peak time only 0.2 (i.v.) and 0.08% (p.o.) of the dose crossed the placenta. Blood levels were always lower than milk concentrations. Preferentially metabolites were excreted with the milk. After a 20-hour suckling period of orally dosed dams, 0.2% of the dose was recovered in the combined tissues of 6 suckling pups.

Administration, Oral↗
PubMed1991

Tissue distribution, metabolism, and elimination of perfluorooctanoic acid in male and female rats.

The elimination, tissue distribution, and metabolism of [1-14C]perfluorooctanoic acid (PFOA) was examined in male and female rats for 28 days after a single ip dose (9.4 mumol/kg, 4 mg/kg). A sex difference in urinary elimination of PFOA-derived 14C was observed. Female rats eliminated PFOA-derived radioactivity rapidly in the urine with 91% of the dose being excreted in the first 24 hr. In the same period, male rats eliminated only 6% of the administered 14C in the urine. The sex-related difference in urinary elimination resulted in the observed difference in the whole-body elimination half-life (t1/2) of PFOA in males (t1/2 = 15 days) and females (t1/2 less than 1 day). Analysis of PFOA-derived 14C in tissues showed that the liver and plasma of male rats and the liver, plasma, and kidney of female rats were the primary tissues of distribution. The relatively high concentration of PFOA in the male liver was further examined using an in situ nonrecirculating liver perfusion technique. It was shown that 11% of the PFOA infused was extracted by the liver in a single pass. The ability of the liver to eliminate PFOA into bile was examined in rats whose renal pedicles were ligated to alleviate sex differences in the urinary excretion of PFOA. In a 6-hr period following IP administration of PFOA, there was no apparent difference in biliary excretion, where both males and females eliminated less than 1% of the PFOA dose via this route. We hypothesized that the sex difference in the persistence of PFOA was due to a more rapid formation of a PFOA-containing lipid (i.e., a PFOA-containing mono-, di-, or triacylglycerol, cholesteryl ester, methyl ester, or phospholipid) in the male rat. Also, the increased urinary elimination of PFOA in females may have been due to increased metabolism to a PFOA-glucuronide or sulfate ester. However, no evidence that PFOA is conjugated to form a persistent hybrid lipid was obtained, nor were polar metabolites of PFOA in urine or bile detected. In addition, daily urinary excretion of fluoride in male and female rats before or after PFOA treatment were similar, suggesting that the parent compound is not defluorinated. Thus, the more rapid elimination of PFOA from female rats is not due to formation of a PFOA metabolite.

Animals↗
PubMed1994

An algorithm and computer program for calculating the mean transit time and distribution rate parameters of generated metabolites undergoing linear tissue distribution and linear or non-linear central elimination.

A method is described for calculating the mean transit time and distribution rate parameters of a generated primary metabolite undergoing linear distribution and linear or non-linear central elimination, and of catenary metabolites with any precursor order. It is also applicable to a drug and its interconversion metabolite and does not require separate administration of the metabolite. The method allows steady-state volume of distribution and distribution clearance of a metabolite to be calculated, provided that the central volume of distribution of the metabolite is known. An algorithm and computer program to implement the proposed method are presented. The calculations require the plasma concentration versus time curves of the metabolite and its precursor. The method is applied to both published and simulated data.

Algorithms↗
PubMed2005

In vivo pharmacokinetic and tissue distribution studies in mice of alternative formulations for local and systemic delivery of Paclitaxel: gel, film, prodrug, liposomes and micelles.

The aim of this study was to increase the understanding on the pharmacokinetic and tissue distribution of paclitaxel as influenced by formulation approach. For this purpose, various formulations investigated in Swiss mice included liposomes, poloxamer 407 gel and chitosan film for subcutaneous route; and water-soluble methacrylate prodrug, liposomes and poloxamer micelles for systemic administration. During this study, the currently marketed formulation of Cremophor EL of paclitaxel was used as the reference. A highest plasma concentration following intravenous administration of paclitaxel was observed for rigid and 'Stealth((R))' liposomes containing the prodrug while, least was for covalently incorporated paclitaxel micelles. Further, poloxamer micelles demonstrated both the highest mean residence time of 7.34 h and volume of distribution (VSS=4.82 and VZ=5.87 L/kg) for paclitaxel. This was followed by prodrug loaded 'Stealth' liposomes, which showed a mean residence time of 4.96 h but were least distributed into apparent physiological volume (VSS=2.12 and VZ=3.16 L/kg). These results clearly signify the role of formulation/excipient in drug disposition and possible interactions. Importantly, due to decrease in the clearance rate of drug, the area under curve values of paclitaxel increased by 1.64- and 2.5-fold for micellar and prodrug loaded 'Stealth' liposomal formulations, respectively over reference formulation. While thermoreversible gels served to decrease plasma concentration of paclitaxel (8-fold) after subcutaneous administration, systemic levels were totally absent after implantation of films. In tissue distribution studies, maximum percent of paclitaxel was observed in liver for reference formulation, conventional liposomes and micelles whereas highest levels of prodrug and 'Stealth((R))' liposomes were in kidney and spleen, respectively. The novel formulations significantly altered tissue accumulation profiles of paclitaxel relative to the reference formulation, for example, reduction in uptake by heart from liposomes and micelles, as well as the major recognition mechanism for elimination. It is proposed that a combination therapy with liposomes and micelles of paclitaxel for systemic delivery along with implantation of chitosan film for local delivery, may serve not only to improve patient compliance by obliterating the need to administer Cremophor EL, but also increase patient survival.

Animals↗
PubMedDate not supplied

[Comparative study of the tissue distribution of two beta-mimetics: clenbuterol and salbutamol in the dog].

Especially because of their physico-chemical properties, and in particular of their lipo-solubility, it was interesting to compare the tissue distribution of two beta 2 sympathomimetics: the clenbuterol and the salbutamol. The study was realised after a direct intravenous administration of clenbuterol chlorhydrate (5 micrograms/kg) and one of salbutamol sulfate (50 micrograms/kg) given to a dog. In a first time, the determination by mass-spectrometry of the two drugs in the plasma allows the pharmacokinetic study in dogs. After a three days wash out, this same experience was repeated. The animals are sacrificed and the assays of the two beta 2 sympathomimetics were effected in lung, bronchial, muscle, heart and brain tissue samples. The tissue distribution was different for clenbuterol and salbutamol and had to be considered as factors of selectivity in the sympathomimetic beta 2 activity. Nervous central diffusion of clenbuterol is higher than salbutamol but cardiac distribution is very important for salbutamol.

Albuterol↗
PubMed2003

Cadaver-assessed validity of anthropometric indicators of adipose tissue distribution.

Although the waist-to-hip ratio (WHR) has emerged as the best anthropometric indicator of the body's adipose tissue distribution, it has never been directly validated. Waist and hip girths, and triceps and subscapular skinfold thickness were measured in 12 male and 13 female cadavers aged 55-94 y. Adipose tissue from the upper limbs, lower limbs, subcutaneous trunk and intra-abdominal regions was then separated by dissection and weighed. Adipose volumes were also determined by hydrostatic weighing. The following adipose tissue mass ratios (and corresponding volume ratios) were derived: trunk to sum of lower limbs, trunk to sum of upper and lower limbs, intra-abdominal to sum of lower limbs and intra-abdominal to sum of upper and lower limbs. Centrality index (CI-subscapular-to-triceps skinfold ratio) and WHR were regressed on the tissue mass and volume ratios of the 25 cadavers. WHR was significantly related to mass and volume ratios for the 12 men (R2=36.0-57.5%, P<0.05), except for intra-abdominal to sum of upper and lower limbs (R(2)=26.3%, P=0.09), but none of these relations was significant in the women. CI was significantly related to all mass and volume ratios only for men and women combined (R(2)=16.2-21.8%, P<0.05). The WHR was better related to all mass and volume ratios than the CI. These results, especially the strong association between WHR and the ratio of intra-abdominal to lower limb adipose masses (R(2)=35.4%, P=0.002), demonstrate a clear relation between the selected anthropometric variables (hip and waist girths, and subscapular and triceps skinfolds) and adipose tissue distribution, thus validating the use of WHR as an important predictor of health risk.

Abdomen↗
PubMed1982

[Evaluation of the clinical effect and tissue distribution of piperacillin in the field of obstetrics and gynecology].

Piperacillin (PIPC) was administered to patients with obstetrical and gynecological infectious diseases and we studied its clinical effect and tissue distribution. 1. Clinical results. PIPC was administered to 26 patients at a dose of 2--4 g per day (twice a day) by dripping infusion over a period of 3--10 days (total 8--30 g). These included 16 cases with intrauterine infection, 1 with adnexitis, 4 with pelvic inflammatory disease and 5 with infections of the external genitalia. The clinical results were excellent in 11 cases, good in 13 cases and poor in 2 cases so that the overall efficacy rate was 92.3%. For bacteriological study 33 strains were isolated from 20 patients. These included Gram positive bacteria (6 strains), Gram negative bacteria (23 strains) and anaerobes (4 strains). After PIPC treatment 32 strains (including S. epidermidis 4 strains, E. coli 12 strains, K. pneumoniae 3 strains, E. aerogenes 2 strains, P. aeruginosa 2 strains and anaerobes 4 strains, etc.) disappeared except for 1 strain of K. pneumoniae which persisted. The disappearance rate was 97.0%. The only side effect observed was a slight case of malaise during the first administration day, however the relationship between the appearance of this symptom and the drug was unclear. No adverse reaction in laboratory findings was observed. 2. Tissue distribution. We determined the tissue concentration from 90 to 240 minutes after dripping infusion for 1 hour at a dose of 2 g. PIPC concentrations in these tissues including the endometrium, myometrium, cervix uteri, portio vaginalis, oviduct and ovary showed the highest level (18.0--11.7 micrograms/g) at 90 minutes after the beginning of administration. These values were 48.6--31.6% in respect to the uterine arterial blood level (37 micrograms/ml at 90 minutes after infusion).

Adult↗
PubMed1989

Quantitative whole-body autoradiographic determination of tacrine tissue distribution in rats following intravenous or oral dose.

Tacrine (1,2,3,4-tetrahydro-9-acridinamine) has been employed in diverse clinical situations but has recently been of considerable interest for the treatment of cognitive deficits associated with senile dementia (Alzheimer's disease). The present studies examined tissue distribution of radiolabeled tacrine by quantitative whole-body autoradiography. Tacrine radioequivalents were widely distributed to tissue following iv or peroral dose, with an apparently prolonged absorption phase following po dose. The presence of high levels of activity in kidneys and ureters indicates a major role for urinary excretion, but there is also evidence for biliary excretion and direct secretion of compound or metabolites into the intestinal lumen. Tacrine was rapidly taken up into the brain and demonstrated regional localization to cortex, hippocampus, thalamus, and striatum. Although the inhibition of acetylcholinesterase by tacrine is well documented, regional uptake in brain did not correlate consistently with distribution of the enzyme, supporting suggestions by others that the alleged action of tacrine in treatment of senile dementia may be by mechanisms other than cholinesterase inhibition.

Administration, Oral↗
PubMed1990

Tissue distribution of [18F]-5-fluorouracil in mice: effects of route of administration, strain, tumour and dose.

In a study investigating the usefulness of 5-fluorouracil labelled with fluorine 18 [( 18F]-5-FU) in cancer chemotherapy, the tissue distribution of the radiolabel was determined in mice at 2, 4 and 6 h after administration by varying several parameters such as the mode of administration, the strain of mouse, the presence of a tumour and the total dose of 5-FU. The tissue distribution of fluorine 18 after i.p. injection pointed to an altered behaviour of the drug and/or its metabolites when compared with values obtained after i.v. injection, but no difference was found in the accumulation of radiolabel in the tumour. A comparison of non-tumour-bearing BALB/c and C57Bl/6 mice revealed that the latter showed a higher radiolabel accumulation of the drug and its metabolites in the liver, kidney, intestines and coecum (P less than 0.05 at 2 and 4 h). In tumour-bearing mice, especially at 2 h, the tissue accumulation of radiolabel was found to be significantly higher than in non-tumour-bearing controls (in BALB/c mice bearing colon 26 carcinoma, P less than 0.05 for all tissues; in C57Bl/6 mice bearing colon 38 carcinoma, P less than 0.05 for the blood, lung, liver, kidney, large intestines, coecum and muscle). Finally, a comparison of injections of a tracer dose of [18F]-5-FU (2.5 mg/kg) vs a therapeutic dose (100 mg/kg) revealed only small differences in the accumulation of fluorine 18 in the liver and kidney.

Animals↗
PubMed2006

Absorption, tissue distribution and excretion of pelargonidin and its metabolites following oral administration to rats.

Recent reports have demonstrated various cardiovascular and neurological benefits associated with the consumption of foods rich in anthocyanidins. However, information regarding absorption, metabolism, and especially, tissue distribution are only beginning to accumulate. In the present study, we investigated the occurrence and the kinetics of various circulating pelargonidin metabolites, and we aimed at providing initial information with regard to tissue distribution. Based on HPLC and LC-MS analyses we demonstrate that pelargonidin is absorbed and present in plasma following oral gavage to rats. In addition, the main structurally related pelargonidin metabolite identified in plasma and urine was pelargonidin glucuronide. Furthermore, p-hydroxybenzoic acid, a ring fission product of pelargonidin, was detected in plasma and urine samples obtained at 2 and 18 h after ingestion. At 2 h post-gavage, pelargonidin glucuronide was the major metabolite detected in kidney and liver, with levels reaching 0.5 and 0.15 nmol pelargonidin equivalents/g tissue, respectively. Brain and lung tissues contained detectable levels of the aglycone, with the glucuronide also present in the lungs. Other tissues, including spleen and heart, did not contain detectable levels of pelargonidin or ensuing metabolites. At 18 h post-gavage, tissue analyses did not reveal detectable levels of the aglycone nor of pelargonidin glucuronides. Taken together, our results demonstrate that the overall uptake of the administered pelargonidin was 18 % after 2 h, with the majority of the detected levels located in the stomach. However, the amounts recovered dropped to 1.2 % only 18 h post-gavage, with the urine and faecal content constituting almost 90 % of the total recovered pelargonidin.

Absorption↗
PubMed2003

The attenuated sopB mutant of Salmonella enterica serovar Typhimurium has the same tissue distribution and host chemokine response as the wild type in bovine Peyer's patches.

Salmonella enterica serovar Typhimurium is an important cause of enteric infections in farm animals and it is one of the most frequent food borne infections worldwide. Serovar Typhimurium lacking the sopB gene is attenuated for induction of host inflammatory response and fluid accumulation into the intestinal lumen, which correlates with clinical diarrhea. SopB is an inositol phosphate phosphatase, but its exact role in the pathogenesis of salmonellosis is still unclear. We employed the bovine ileal ligated loop model to compare the tissue distribution of a sopB mutant and its wild type parent serovar Typhimurium. Sections of the Peyer's patches were histologically processed and immuno-stained for detection of serovar Typhimurium. In addition, samples were processed for transmission electron microscopy, and the profile of expression of host chemokine and cytokine responses was assessed. Ultrastructurally both strains had the same ability to invade intestinal epithelial cells. No differences were detected in the tissue distribution of the sopB mutant and the wild type organism and both strains elicited the same profile of chemokines and pro-inflammatory cytokines. In conclusion, our results indicate that the attenuation of the sopB mutant is associated with pathogenic mechanisms other than invasion and distribution in host intestinal tissues.

Animals↗
PubMed1990

Body composition and tissue distribution from birth to 14 months for three biological types of beef heifers.

Thirty-four heifers were sampled randomly from each of the Hereford (He), Charolais (Ch) and Simmental (Si) herds at the U.S. Meat Animal Research Center at 2 d to 14 mo of age to examine body chemical composition and tissue distribution. Six heifers per breed were slaughtered after calorimetry at 2 d, 3 mo, 7 mo, 10 mo and 14 mo of age, and four others at 8 mo, to measure weight of empty body (EBW), water, fat, ash and protein as residual, in four fractions: carcass (CAR), head, hide and shanks (HHS), gastrointestinal tract plus internal fat (GIF) and visceral organs plus blood (VOB). Fasted live weight from birth to 14 mo increased from 39 to 414 kg for Ch, 38 to 385 kg for Si and 33 to 356 kg for He. Corresponding mean composition of EBW increased from 58 to 67% CAR and from 7 to 13% GIF but declined from 26 to 15% HHS and from 9 to 6% VOB. The water content of EBW declined from 73 to 51%, protein from 20 to 18% and ash from 4.3 to 3.5%, whereas fat increased from 3 to 28% and protein content of fat-free OM increased from 22% to 26%. Composition of CAR was similar to EBW but fat content increased more with age in GIF, less in HHS and least in VOB. Distribution of fat-free tissue changed from 58 to 66% in CAR, 26 to 18% in HHS, 7 to 8% in GIF and 9 to 8% in VOB. The EBW of Ch contained more CAR but less HHS than EBW of Si and HE. The EBW of Si and Ch contained more water and protein and less FAT than EBW of HE. The fatter He had proportionately less of their fat-free tissue in CAR (63%) and more in HHS (21%) and GIF (9%) than the Ch (66, 19, and 8%), with Si (64, 20 and 8%) intermediate. These age and breed differences in composition and tissue distribution may explain some of the variation in maintenance requirements.

Animals↗
PubMed1993

Tissue distribution of somatostatin receptor subtype messenger ribonucleic acid in the rat.

The tissue distribution of mRNA encoding five somatostatin receptor subtypes, SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5, was determined in adult rat tissues by solution hybridization/nuclease protection analysis using sequence-specific cRNA probes. In the central nervous system, SSTR1 and SSTR2 mRNA were expressed widely, with highest levels in hippocampus, hypothalamus, cortex, and amygdala and expression of both isoforms in cerebellum and spinal cord. Expression of SSTR3 was also widespread, occurring in all brain regions examined, with the highest level of expression in the cerebellum. SSTR4 mRNA was detected in most brain regions, with highest levels occurring in the hippocampus, cortex, and olfactory bulb. No detectable levels were found in cerebellum. SSTR5 showed a unique pattern of expression in the central nervous system, being found primarily in the hypothalamus and preoptic area. In peripheral tissues, high levels of SSTR1 and SSTR2 mRNA were found in pituitary and spleen. SSTR1 mRNA was also found in the heart and intestine, SSTR2 was detected in pancreas, and both isoforms were expressed in stomach. Expression of SSTR3 was noted in heart, liver, stomach, intestine, kidney, spleen, and pituitary. The patterns of expression were similar for SSTR4 and SSTR3 mRNA; however, SSTR4 was not expressed in liver. SSTR5 was expressed predominantly in the pituitary, but detectible levels were observed in spleen and intestine. Thus, the SSTR subtype mRNA showed both a tissue-specific and overlapping pattern of expression. Taken together with SSTR-specific signal transduction systems, this probably explains the diverse physiological actions of somatostatin.

Animals↗
PubMed2005

How does soft tissue distribution affect anteversion accuracy of the palpation procedure in image-free acetabular cup navigation? An ultrasonographic assessment.

Navigation of the acetabular cup in total hip replacement (THR) is used to improve the reproducibility of acetabular component positioning. When the palpation of anatomic landmarks, which is necessary to determine the pelvic coordinate system, is performed epicutaneously, the question as to how uneven soft tissue distribution can influence navigation accuracy arises. To obtain data, the questionable soft tissue thickness was measured in 72 patients scheduled for THR. In addition, distances between the landmarks were recorded. On the basis of this information, we were able to calculate the expected misinterpretation of the anteversion given by a navigation system for each patient. The calculations suggest that a navigation system would have underestimated the anteversion on average by 2.8 degrees +/- 1.8 degrees. The median of anteversion misinterpretation was 2.4 degrees and its 95% confidence interval was calculated to be 2.2 degrees -3.0 degrees. No correlation with substantial significance between anteversion misinterpretation and the patients' biometrical data could be found. According to the current knowledge, acetabular cups in THR should be positioned within a range of 30 degrees -50 degrees of inclination and 10 degrees -30 degrees of anteversion. In comparison with these permitted +/- 10 degrees windows, the amount of misinterpretation that was found due to uneven soft tissue distribution seems to be acceptable.

Acetabulum↗
PubMed2005

The rat Na+-sulfate cotransporter rNaS2: functional characterization, tissue distribution, and gene (slc13a4) structure.

Inorganic sulfate is essential for numerous functions in mammalian physiology. In the present study, we characterized the functional properties of the rat Na+-sulfate cotransporter NaS2 (rNaS2), determined its tissue distribution, and identified its gene (slc13a4) structure. Expression of rNaS2 protein in Xenopus oocytes led to a Na+-dependent transport of sulfate that was inhibited by phosphate, thiosulfate, tungstate, selenate, oxalate, and molybdate, but not by citrate, succinate, or DIDS. Transport kinetics of rNaS2 determined a K(M) for sulfate of 1.26 mM. Na+ kinetics determined a Hill coefficient of n=3.0+/-0.7, suggesting a Na+:SO4 (2-) stoichiometry of 3:1. rNaS2 mRNA was highly expressed in placenta, with lower levels found in the brain and liver. slc13a4 maps to rat chromosome 4 and contains 17 exons, spanning over 46 kb in length. This gene produces two alternatively spliced transcripts, of which the transcript lacking exon 2 is the most abundant form. Its 5' flanking region contains CAAT- and GC-box motifs and a number of putative transcription factor binding sites, including GATA-1, SP1, and AP-2 consensus sequences. This is the first study to characterize rNaS2 transport kinetics, define its tissue distribution, and resolve its gene (slc13a4) structure and 5' flanking region.

Animals↗
PubMed1985

Tissue distribution and magnetic resonance spin lattice relaxation effects of gadolinium-DTPA.

Gadolinium-DTPA complex (Gd-DTPA) is a potential clinical magnetic resonance (MR) contrast agent that enhances images primarily by decreasing spin-lattice relaxation time (T1) in tissues in which it localizes. This study was designed to determine the immediate tissue distribution of intravenously administered Gd-DTPA in selected organs of interest as a function of administered dose and tissue Gd-DTPA concentration. An intravenous bolus of Gd-DTPA with a tracer quantity of Gd-153 was administered to three groups of rabbits at the following doses: 0.01 mM/kg (n = 6); 0.05 mM/kg (n = 6); 0.10 mM/kg (n = 6). A control group received sham injections. Five minutes after Gd-DTPA was administered, all animals were killed; samples of serum, lung, heart, kidney, liver, and spleen were analyzed in a 0.25 T MR spectrometer to measure T1, and then in a gamma well counter to determine tissue concentration of Gd-DTPA. Tissue distribution (per cent dose/tissue weight in g) at five minutes after injection was proportionally constant over the range of doses given. Tissue concentration varied linearly with injected dose (r greater than 0.98 for all tissues). Relaxation rate (1/T1) varied linearly with injected dose and with tissue Gd-DTPA concentration (r greater than 0.97 for all tissues). The order of tissue relaxation rate response to a given dose was: kidney greater than serum greater than lung greater than heart greater than liver greater than spleen. We conclude that because of its extracellular distribution and linear relaxation rate versus concentration relationship, Gd-DTPA enhancement in MR images may be a good marker of relative organ perfusion.

Animals↗
PubMed1982

Pharmacokinetics and tissue distribution of metronidazole in the new born infant.

Metronidazole pharmacokinetics and tissue distribution were studied in 11 infants varying in gestational age from 28 to 40 weeks. Elimination half-life was inversely related to gestational age, and ranged from 22.5 to 109 hours. Hepatic hydroxylation of metronidazole was not evident in infants less than 35 weeks' gestation, unless they had been exposed prenatally to betamethasone. A dosage schedule of 15 mg/kg intravenously as an initial single dose is proposed, and will provide adequate therapeutic levels for 48 hours in the preterm infant and for 24 hours in the term infant. Subsequently a dose of 7.5 mg/kg/12 hours is suggested for the first week of life.

Bacterial Infections↗