Phase I study of granulocyte colony-stimulating factor in patients with transitional cell carcinoma of the urothelium.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered at a dose of 1-60 micrograms/kg of body weight to 22 patients with transitional cell carcinoma before chemotherapy as part of a Phase I/II study. In all patients, a specific dose-dependent increase in the absolute neutrophil count (ANC) of 1.8-12 fold was seen. In addition, this augmentation in the ANC was accompanied by an increase in leukocyte alkaline phosphatase, a marker of secondary granule formation. In six of eight patients analyzed, an increase in bone marrow myeloid to erythroid cell ratio was seen. Day 14 peripheral blood cell derived colony forming unit granulocyte macrophage were also increased by day 6 of rhG-CSF treatment. Circulating levels of eosinophils and basophils were unchanged; however, a 10-fold increase in monocytes was observed in patients treated at the highest doses. There was also a small increase in CD3+ lymphocytes that was not dose dependent. Hemoglobin, hematocrit, and platelet count remained near baseline throughout the period of rhG-CSF administration. These findings demonstrate that rhG-CSF is a potent stimulus for normal neutrophil proliferation and maturation.     

31例高龄脑出血临床特点分析

对３１例高龄脑出血病人的发病季节，病因，起病状态，发病早期血压变化，ＣＴ或ＭＲＩ扫描结果以及临床特点进行分析，结果说明４月份至８月份发病及活动中发病较高，男性发病高于女性，左右半球出血的发生率差异不大，出血部位，出血量的大小以及并发症与疾病的转归有着密切的关系。     

MPXI and early neutrophilia: New potential therapeutic biomarkers for recombinant human granulocyte colony-stimulating factor

We evaluated the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) given after myelosuppressive chemotherapy in 15 cancer patients. No severe neutropenia (absolute neutrophil count, ANC < 0.5 × 10³/μL) was noticed in 10 rhG-CSF primary prophylactic patients, but was noticed in two of five rhG-CSF secondary prophylactic patients. Neutrophilia characterized by shift to the left occurred within 24 hours after starting rhG-CSF prophylaxis. Thereafter, conversion to normal level occurred within 24 hours. The peak of neutrophilia occurred earlier in the primary group than in the secondary prophylactic group. The detection of myeloperoxidase (MPO) using flow cytochemistry blood autoanalyzer (Technicon^R H*1) was evaluated as mean peroxidase index (MPXI). Leukocyte alkaline phosphatase (LAP) using the method of Kaplow (Am J Clin Pathol 39:439–449, 1963) was recorded as LAP score. There was a statistically significant elevation of MPXI in the primary group over the secondary prophylactic patients. The LAP activity was in normal range. There was a slightly decreased red blood cell (RBC) count, hemoglobin (Hb), and platelet count. In conclusion, rhG-CSF induced neutrophilia with efficient enzymatic activity. These findings demonstrate the value of rhG-CSF in patients receiving chemotherapy. MPXI and early neutrophilia may serve as a potential biomarker of therapeutic efficacy of rhG-CSF. J. Clin. Lab. Anal. 41–46, 1998. © 1998. Wiley-Liss, Inc.     

Deficient flavoprotein component of the NADPH-dependent O2-.-generating oxidase in the neutrophils from three male patients with chronic granulomatous disease.

The NADPH-dependent O2-.-generating oxidase in subcellular fractions from the neutrophils of three male patients with chronic granulomatous disease was compared with the corresponding preparations from normal neutrophils. The oxidase from normal neutrophils contained flavin adenine dinucleotide in an approximately 0.9:1 molar ratio with cytochrome b559. Each of the three chronic granulomatous disease patients had decreased amounts of the flavoprotein component of the oxidase fraction. The oxidase from two chronic granulomatous disease patients had undetectable amounts of cytochrome b559 whereas the third patient had a normal content of cytochrome b559, which was spectrally indistinguishable from the normal. The intrinsic cytochrome b559 in the oxidase fraction from stimulated neutrophils of the latter chronic granulomatous disease patient was not reduced by NADPH under anaerobic conditions, in distinction with the previously reported reduction of the normal cytochrome b559 under identical conditions. We conclude that the flavoprotein component of the oxidase may mediate transfer of electrons from NADPH to the cytochrome b559 in normal neutrophils, and that deficiency of this flavoprotein is associated with the chronic granulomatous disease phenotype in the three patients studied.     

Effects of Renal Function on Pharmacokinetics of Recombinant Human Granulocyte Colony-Stimulating Factor in Lung Cancer Patients

Animal studies suggest that the kidney is involved in the elimination of recombinant human granulocyte colony-stimulating factor (rhG-CSF), which is used for patients with neutropenia during cancer chemotherapy. Since anticancer drugs induce nephrotoxicity, it is important to clarify the role of the kidney in the pharmacokinetics of rhG-CSF in cancer patients. Our study was designed to evaluate the relationship between the pharmacokinetics of rhG-CSF and renal function in lung cancer patients compared to the absolute neutrophil count (ANC). The pharmacokinetic studies were conducted with 25 lung cancer patients. Following chemotherapy using platinum-based compounds, a bolus 5 microg of rhG-CSF/kg of body weight was intravenously injected from the first day of leukopenia or neutropenia. Pharmacokinetic parameters were estimated by fitting the concentration in serum-time data to a two-compartment model according to the population pharmacokinetics and the Bayesian method. Creatinine clearance (CL(CR)) was predicted by the Cockcroft-Gault formula. rhG-CSF clearance (CL(G-CSF)) correlated significantly with the ANC (r = 0.613; P < 0.001) and CL(CR) (r = 0.632; P < 0.001). Multiple linear regression analysis showed that the combination of the ANC and CL(CR) accounted for 57.4% of the variation of CL(G-CSF). In patients with an ANC of <1,000/microl, CL(CR) accounted for 72.9% of the variation of CL(G-CSF) (P < 0.001). Our findings suggest that renal function and neutrophil counts correlate with CL(G-CSF) and that the role of renal function in eliminating rhG-CSF is important in lung cancer patients with neutropenia.     

伊曲康唑联合重组人粒细胞集落刺激因子治疗中性粒细胞减少的血液病患者侵袭性真菌感染的疗效及安全性评价

目的 评价伊曲康唑联合重组人粒细胞集落刺激因子（rhG-CSF）治疗中性粒细胞减少的血液病患者合并侵袭性真菌感染的临床疗效及安全性.方法 回顾性分析2007年1月至2011年12月收治的103例血液病合并真菌感染的患者,治疗期间72例患者出现粒细胞缺乏,其中44例患者应用伊曲康唑联合rhG-CSF治疗（治疗组）,28例患者单独应用伊曲康唑治疗（对照组）.结果 治疗组患者有效率为72.73％,对照组为46.43％（P＜0.05）;中性粒细胞≤500/mm3且≥100/mm3的患者抗真菌治疗有效率明显高于中性粒细胞≤100/mm3的患者（P＜0.05）;粒缺持续时间≤10 d的抗真菌治疗有效率明显低于粒缺持续时间＜10 d的患者（P ＜0.05）;72例患者中确诊9例、临床诊断33例、拟诊30例;确诊组有效率低于临床诊断与拟诊组（P＜0.05）,抢先性治疗组（87.50％）和经验性治疗组（64.00％）的有效率均明显高于目标性治疗组（34.78％）,差异有统计学意义（P均＜0.05）.结论 伊曲康唑联合rhG-CSF治疗中性粒细胞减少的血液病患者真菌感染是有效安全的;中性粒细胞减少的程度和时间是影响真菌治疗效果的重要因素.     

Recombinant human granulocyte colony-stimulating factor. Effects on hematopoiesis in normal and cyclophosphamide-treated primates

We examined the in vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in primates (cynomolgus monkeys) treated with subcutaneous doses of rhG-CSF for 14-28 d. A dose-dependent increase in the peripheral white blood cells (WBC) was seen, reaching a plateau after 1 wk of rhG-CSF treatment. The elevation of WBC was due to an increase in the absolute neutrophil count. These results demonstrate that rhG-CSF is a potent granulopoietic growth and differentiation factor in vivo. In cyclophosphamide (CY)-induced myelosuppression, rhG-CSF was able to shorten the time period of WBC recovery in two treated monkeys to 1 wk, as compared to more than 4 wk for the control monkey. Its ability to significantly shorten the period of chemotherapy-induced bone marrow hypoplasia may allow clinicians to increase the frequency or dosage of chemotherapeutic agents. In addition, the increase in absolute numbers of functionally active neutrophils may have a profound effect in the rate and severity of neutropenia-related sepsis. Furthermore, the activities reported here indicate a potential role for rhG-CSF in the treatment of patients with myelodysplastic syndrome, congenital agranulocytosis, radiation-induced myelosuppression, and bone marrow transplantation.     

Pharmacokinetics and pharmacodynamics of granulocyte-macrophage colony-stimulating factor and zidovudine in patients with AIDS and severe AIDS-related complex.

Granulocytopenia is a complication of human immunodeficiency virus disease, as well as a toxic manifestation of zidovudine therapy. To evaluate pharmacokinetic and pharmacodynamic relationships, 11 AIDS-AIDS-related complex patients who had developed zidovudine-associated granulocytopenia (mean absolute neutrophil count, 1,077/mm3) were examined after addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) to zidovudine. GM-CSF was administered as a daily (1.0 or 0.3 micrograms/kg) or every-other-day (0.3 micrograms/kg) subcutaneous dose over a 28-day period. Zidovudine was continued at the same daily dosage as was previously being administered. Of 11 patients, 7 (1.0 micrograms/kg, n = 5; 0.3 micrograms/kg, n = 2) had a pharmacologic response to GM-CSF with an increase to a mean absolute neutrophil count of 3,189 cells per mm3 at 4 weeks (P < 0.05). The peak concentration of GM-CSF in plasma ranged from 11.5 to 84.4 pg/ml, and the time to peak ranged from 1 to 3 h. No correlation between GM-CSF disposition and hematologic response was noted. A decreased plasma zidovudine-glucuronide/zidovudine ratio was noted after 1 week of GM-CSF, and an increase in the area under the plasma concentration-versus-time curve for zidovudine was found in three patients after 4 weeks. Low doses of GM-CSF can raise the granulocyte count in patients with zidovudine-induced neutropenia. The use of GM-CSF and zidovudine may represent a viable treatment option for persons with human immunodeficiency virus infection who develop neutropenia while receiving zidovudine but do not tolerate alternative nucleoside analogs. Further studies are needed to assess the complex interaction between these two agents.     

Close Association between Clearance of Recombinant Human Granulocyte Colony-Stimulating Factor (G-CSF) and G-CSF Receptor on Neutrophils in Cancer Patients

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is used to counter chemotherapy-induced neutropenia. Our previous study showed an inverse correlation between serum rhG-CSF levels and the number of circulating neutrophils in cancer patients (H. Takatani, H. Soda, M. Fukuda, M. Watanabe, A. Kinoshita, T. Nakamura, and M. Oka, Antimicrob. Agents Chemother. 40:988–991, 1996). The aim of this study was to clarify the relationship between rhG-CSF clearance and G-CSF receptors on circulating neutrophils. In five cancer patients receiving chemotherapy, a bolus dose of rhG-CSF (5 μg/kg) was injected intravenously during defined phases of posttreatment neutropenia and neutrophilia. Serum rhG-CSF levels were measured by a chemiluminescence enzyme immunoassay and analyzed by moment analysis. G-CSF receptors on neutrophils were detected by flow cytometry with biotinylated rhG-CSF. rhG-CSF clearance was significantly higher at neutrophilia than at neutropenia (1,497 ± 132 versus 995 ± 266 ml/h; P < 0.01). The percentage of G-CSF receptor-positive neutrophils, reflecting the number of G-CSF receptors per cell, was low at neutropenia without rhG-CSF therapy (44.5% ± 22.1%) and high at neutrophilia with rhG-CSF therapy (73.0% ± 11.4%; P < 0.01). rhG-CSF clearance closely correlated with the percentage of G-CSF receptor-positive neutrophils (r² = 0.91; P < 0.0001) and neutrophil count (r² = 0.72; P < 0.005). Our results indicate that, in cancer patients receiving chemotherapy, rhG-CSF increases the number of G-CSF receptors per cell as well as circulating neutrophil counts, resulting in modulation of its own clearance.     

rhG-CSF对急性白血病化疗后中性粒细胞形态、功能、表型的影响

为了探讨急性白血病病人化疗后应用rhG-CSF对中性粒细胞形态、功能及表型变化的影响,采用油镜下观察细胞形态,过氧化氢释放法、琼脂糖测定法、免疫荧光技术和流式细胞术检测中性粒细胞的吞噬、趋化及氧化代谢功能;采用免疫荧光技术和流式细胞分析检测中性粒细胞表型.结果表明：应用rhG-CSF后,中性粒细胞胞浆内＂中毒＂颗粒数、空泡数和Dohle小体数增加;化疗后病人中性粒细胞吞噬、趋化及氧化代谢功能明显低于正常组,用rhG-CSF后功能均增强,基本接近正常组甚至超出;用rhG-CSF前中性粒细胞CD64、CD62L的表达明显高于正常对照组,用G-CSF后CD64表达上调,CD62L表达显著下调;CD16、CD32、CD14和CD11b则无明显改变.结论：急性白血病病人化疗后应用rhG-CSF可引起中性粒细胞形态、功能及表型出现变化,进一步增强机体的抗感染能力.     

Levels of recombinant human granulocyte colony-stimulating factor in serum are inversely correlated with circulating neutrophil counts.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is effective in countering chemotherapy-induced neutropenia. However, serum rhG-CSF levels cannot be maintained throughout the course of rhG-CSF therapy. The drop in serum rhG-CSF levels may vary with the duration of rhG-CSF administration or with the circulating neutrophil counts. We investigated the relationship between serum G-CSF levels and circulating neutrophil counts and the pharmacokinetics of rhG-CSF for patients with lung cancer who had been treated with myelosuppressive chemotherapy and then with subcutaneous rhG-CSF (lenograstim, 2 micrograms per kg of body weight per day). Twelve patients were randomly assigned to four groups with different rhG-CSF therapy schedules. Serum G-CSF levels were measured by an enzyme immunoassay method. Serum G-CSF levels during the rhG-CSF therapy greatly exceeded endogenous G-CSF levels and were mainly due to the presence of exogenous rhG-CSF rather than increased levels of endogenous G-CSF. Despite the duration of rhG-CSF administration, serum G-CSF levels during rhG-CSF therapy were inversely correlated with circulating neutrophil counts (r2 = 0.73, P < 0.0001). The value for the area under the concentration-time curve of rhG-CSF on the day of neutrophilia was lower than that on the day of neutropenia (P < 0.05). Our results suggest that the fall in serum G-CSF levels during rhG-CSF therapy may result from increased clearance and/or decreased absorption of rhG-CSF, two processes related to circulating neutrophil counts.     

Increased granulocyte colony-stimulating factor responsiveness but normal resting granulopoiesis in mice carrying a targeted granulocyte colony-stimulating factor receptor mutation derived from a patient with severe congenital neutropenia.

The role of mutations of the granulocyte colony-stimulating factor receptor (G-CSFR) in the pathogenesis of severe congenital neutropenia (SCN) and the subsequent development of acute myeloid leukemia (AML) is controversial. Mice carrying a targeted mutation of their G-CSFR that reproduces the mutation found in a patient with SCN and AML have been generated. The mutant G-CSFR allele is expressed in a myeloid-specific fashion at levels comparable to the wild-type allele. Mice heterozygous or homozygous for this mutation have normal levels of circulating neutrophils and no evidence for a block in myeloid maturation, indicating that resting granulopoiesis is normal. However, in response to G-CSF treatment, these mice demonstrate a significantly greater fold increase in the level of circulating neutrophils. This effect appears to be due to increased neutrophil production as the absolute number of G-CSF-responsive progenitors in the bone marrow and their proliferation in response to G-CSF is increased. Furthermore, the in vitro survival and G-CSF-dependent suppression of apoptosis of mutant neutrophils are normal. Despite this evidence for a hyperproliferative response to G-CSF, no cases of AML have been detected to date. These data demonstrate that the G-CSFR mutation found in patients with SCN is not sufficient to induce an SCN phenotype or AML in mice.     

A long-term study and correlation of lymphocyte and neutrophil function in the patient with burns

Twenty-five patients were studied to determine the effects of thermal injury on neutrophil bactericidal function and superoxide release and on lymphocyte proliferation. Neutrophils in patients with burns had depressed killing of Staphylococcus aureus for more than 150 days after burn injury, but killing of Escherichia coli returned to normal. FMLP-stimulated superoxide release by neutrophils in patients with burns was depressed for over 100 days after burn injury, whereas superoxide release by neutrophils in patients with burns stimulated with serum-opsonized zymosan was depressed for 42 days after burn injury. In patients with burns lymphocyte proliferation, with phytohemagglutinin as a mitogen, was suppressed for up to 85 days after injury, then returned to normal. The mixed lymphocyte response was suppressed up to 170 days after injury.     

Recombinant human tumor necrosis factor-alpha. Regulation of N-formylmethionylleucylphenylalanine receptor affinity and function on human neutrophils.

Preincubation of neutrophils with recombinant human tumor necrosis factor-alpha (rH TNF-alpha) enhanced the subsequent release of superoxide anion in response to various concentrations of N-formylmethionylleucylphenylalanine (FMLP). Enhanced superoxide anion production was evident by 5 min and had reached a plateau by 15 min. Not only was the total amount of superoxide anion released greater, but the rate of release was also enhanced threefold by rH TNF-alpha. In contrast, rH TNF-alpha reduced or abolished neutrophil locomotion under agarose in response to a gradient of FMLP. Binding studies of f-Met-Leu-[3H]Phe to purified human neutrophils revealed a heterogeneous binding to unstimulated cells. The high affinity component consisted of approximately 2,000 sites per cell and had an average Kd of 2 +/- 0.7 nM (n = 4). The low affinity component consisted of approximately 40,000 sites per cell and had an average Kd of 180 +/- 50 nM (n = 4). rH TNF-alpha caused conversion to a linear Scatchard plot showing no significant change in total binding sites but a single Kd of 40 +/- 10 nM (n = 4). These data indicate that rH TNF-alpha may influence neutrophil responses to FMLP by regulating the affinity of FMLP receptors.     

rhG-CSF对140例恶性肿瘤化放疗所致白细胞减少的临床疗效观察

为了观察rhG CSF对恶性肿瘤放化疗所致白细胞减少的疗效 ,对 14 0例恶性肿瘤放化疗所致粒细胞减少的患者用此国产rhG CSF(粒生素 )进行治疗。白细胞 <3.0× 10 9/L或中性粒细胞绝对计数 (ANC) <2 .0× 10 9/L时开始用粒生素 75 μg,皮下注射 ,每日 1次 ,待白细胞 >4 .0× 10 9/L或中性粒细胞绝对计数 >2 .5× 10 9/L时停药。结果表明 :粒生素能使放化疗所致粒细胞减少回升至正常范围 ,平均时间为 4 8天 ,有效率 96 .4 %。结论 :粒生素可以明显减轻放化疗过程中外周血白细胞下降程度 ,缩短白细胞恢复时间 ,且毒副反应轻、安全可靠 ,有利于放化疗的顺利进行。     

大剂量粒细胞集落刺激因子对2.3Gy中子γ射线混合照射比格犬存活和造血重建的影响(英文)

本研究旨在观察大剂量重组人粒细胞集落刺激因子(rhG-CSF)对中子-γ射线混合照射比格犬的治疗作用。13只比格犬用90%裂变中子(n∶γ=10.6∶1)单侧一次照射2.3 Gy。实验分为照射对照(n=4)、对症治疗(n=5)和rhG-CSF治疗(n=4)3组。rhG-CSF治疗组照射后0.5和24小时2次皮下注射rhG-CSF 200μg/kg。结果表明,2.3 Gy 90%裂变中子照射可致重度骨髓型急性放射病,照射后50天3组动物分别活存1/4、3/5和4/4;rhG-CSF给药可使动物存活率由对症治疗组的60%提高至100%。与对症治疗组比较,照射后24小时内2次给予rhG-CSF可缩短中性粒细胞减少持续时间,提高中性粒细胞最低值,并促进其恢复。rhG-CSF治疗组照射后3天外周血有核细胞形成集落数量(CFU-GM、CFU-E和BFU-E)明显增加,为对症治疗组的2-5倍。照射后50天,胸骨病理切片检查结果显示,rhG-CSF治疗动物造血全部恢复正常,而对症治疗组动物仍然存在造血细胞数量严重减少。结论:照射后早期大剂量rhG-CSF 2次皮下注射联合对症治疗可明显促进2.3 Gy裂变中子-γ射线混合照射比格犬造血功能恢复,提高其存活。     

Peripheral blood stem cell collection from healthy donors for allogeneic transplantation

There is great interest in the use of peripheral blood stem cells (PBSC) for allogeneic transplantation, based on the good results seen with autologous PBSC infusion. Reasonable caution exists regarding the use of allogeneic PBSC for transplantation because of donor toxicities due to rhG-CSF administration and the risk of graft-versus-host-disease (GVHD) in the recipient because of the large number of T-cell infused. We present preliminary data on allogeneic PBSC collections and transplantation in ten patients affected by advanced leukemia (eight patients), severe aplastic anemia (one patient) and sickle cell anemia (one patient). Seven donors were HLA-identical siblings, while the other three were mismatched for three, two and one locus, respectively. All donors received rhG-CSF at a dose of 12 micrograms/kg for a mean of 5 days. Leukaphereses were performed with the aim of collecting a minimum of 5 x 10(6)/kg (recipient's weight) CD 34+ cells. Collection timing was determined by monitoring CD 34+ cells in the donor's peripheral blood from the second day of rhG-CSF therapy. The PBSC collections yielded a mean of 10.05 x 10(8) MNCs/kg and of 10.48 x 10(6) CD 34+ cells/kg (recipient's weight). PBSC were immediately infused after collection in patients given myeloablative therapy. Engraftment was observed in each patient at a mean of 13.2 days for an absolute neutrophil count (ANC) more than 0.5 x 10(9)/L and of 26.5 days for a platelet count of more than 20 x 10(9)/L. Eight patients experienced no or moderate acute GVHD, whereas two patients died of grade 4 GVHD, notwithstanding GVHD prophylaxis with cyclosporine and prednisone. Two other patients died of viral and fungal infections, respectively, despite prophylaxis. The remaining six patients are alive between 58 and 430 days after transplant. Our results document that allogeneic PBSC are capable of engraftment after a myeloablative regimen. Controlled trials are necessary to compare the potential benefits of this approach with the results obtained in allogeneic bone marrow transplantation.     

疟疾患者外周血T淋巴细胞亚群检测及临床意义

目的 探讨疟疾患者外周血T淋巴细胞亚群的变化及其临床意义。方法 选取2020年1月～10月期间广州医科大学附属市八医院就诊的49例病人标本,分为疟疾患者组（n=36）和健康对照组（n=13）,采用流式细胞技术检测其外周血T淋巴细胞亚群,比较两组间T淋巴细胞亚群绝对计数与百分比的差异性;将疟疾患者组分为恶性疟组（n=33）与卵形疟组（n=3）,比较两组间T淋巴细胞亚群绝对计数与百分比的差异性;将疟疾患者组分为普通型组（n=30）与重症型组（n=6）,比较两组间T淋巴细胞亚群绝对计数与百分比的差异性;同时比较恶性疟患者治疗前后的T淋巴细胞亚群绝对计数与百分比的差异性。结果 疟疾患者组CD45+(882.21±595.94个/μl),CD3+(636.00±390.84个/μl),CD3+CD4+(363.81±234.90个/μl)和CD3+CD8+(230.92±81.93个/μl)T淋巴细胞绝对计数值均低于健康对照组（2291.15±674.20个/μl,1 680.15±510.72个/μl,934.15±317.80个/μl,615.07±280.14个/μl）,差异具有统计学意义...     

Pharmacokinetics and pharmacodynamics of recombinant human granulocyte-colony stimulating factor after intravenous and subcutaneous administration in the rat

The pharmacokinetics of recombinant human granulocyte-colony stimulating factor (rhG-CSF) (produced by Kirin Brewery Co., Ltd.) in sera was studied after i.v. and s.c. administration into male Sprague-Dawley rats. Arterial blood samples were taken to determine the rhG-CSF concentrations by measuring its activities using a modified [3H]thymidine assay. After the i.v. dose of 100 micrograms/kg, the half-lives were 25 (alpha) and 102 min (beta). Subcutaneous administration at the 100-micrograms/kg dose resulted in a lower peak serum level but, after 2 hr, rhG-CSF level after the s.c. dose was higher than that of the i.v. dose. The bioavailability of the s.c. dose of 100 micrograms/kg was 78%. The effect of rhG-CSF administration in rats was a specific activity on the neutrophil lineage with increase of neutrophils in peripheral blood. Intravenous and s.c. administration of rhG-CSF had identical effects on the peak neutrophil counts in peripheral blood but, at 24 hr after injection, neutrophil counts after the s.c. dose was greater than that of the i.v. dose. These results indicate the close relationship between pharmacokinetics and pharmacodynamics of rhG-CSF in the rats.